drug eluting balloons (deb) - global pipeline analysis, competitive landscape and market forecasts...

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Drug Eluting Balloons (DEB) - Global Pipeline Analysis, Competitive Landscape and Market Forecasts to 2017

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ExecutiveSummary

The GlobalDrug ElutingBalloonsMarket isExpected toNearly Doubleover the NextSeven Years

Drug ElutingBalloon’sPotential toBecome aViableTreatment for aLarge Numberof Indicationsto Drive theMarket

B. Braun,Eurocor andInvatecDominateGlobal DrugEluting BalloonsMarket

Introduction

GlobalDataReportGuidance

MajorCardiovascularIndicationsApproved for DrugEluting Balloons

In-StentRestenosis

Drug ElutingBalloons - GlobalMarketCharacterization

Global DrugEluting BalloonsMarket,Revenue ($m),2003-2010

Global DrugEluting BalloonsMarket,Revenue ($m),2010-2017

Executive Summary

The Global Drug Eluting Balloons Market is Expected to Nearly Double over the Next Seven Years

Figure 1: Drug Eluting Balloons Market, Global, Revenue($m), 2010-2017

Source: GlobalData, Annual Reports, SEC Filings, Investor Presentations, Earning Call Transcripts, Newsand Press Releases, Scientific Journals, Trade Associations, Interviews with Industry Experts and KeyOpinion Leaders (KOLs)

The Drug Eluting Balloons (DEBs) market is expected to grow at a Compound Annual Growth Rate (CAGR) of 8.1% to $127m by 2017. The Percutaneous TransluminalCoronary Angioplasty (PTCA) DEB market is also expected to grow at 8.1% to $103m by 2017. The Percutaneous Transluminal Angioplasty (PTA) DEB market is expectedto grow at a CAGR of 8.2% to reach $24m 2010-2017. The market will be driven by increased physician adoption as long term clinical data is released and as the device isadopted for new indications such as Peripheral Vascular Disease (PVD). The US Food and Drug Administration (FDA) product approvals over the next two to three years arealso expected to boost future uptake future because the US is an important region for the interventional cardiology devices market. DEBs fulfill a huge unmet need in themarket and so adoption is expected to increase at the same rate as physician awareness.

Drug Eluting Balloon’s Potential to Become a Viable Treatment for a Large Number of Indications to Drive the Market

Small Vessel Disease (SVD), bifurcated lesions, In-Stent Restenosis (ISR) and PVD represent nearly a $2 billion market potential. In addition, the complications associatedwith long term antiplatelet therapy such as the risk of bleeding and contraindications limit the use of current interventions. Cost and patient compliance is also a factorpromoting the use of DEBs. The unique value proposition of DEBs such as improving both safety and efficacy for some indications has the potential to create a niche

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Global DrugEluting BalloonsMarket, Volume(Units), 2007-2010 Global DrugEluting BalloonsMarket, Volume(Units), 2010-2017

Global DrugElutingBalloons,MarketDynamics

Drug ElutingBalloons Market,by Country,Revenue ($m),Volume, 2003-2017

Germany DrugEluting BalloonsMarket,Revenue ($m),2003-2010

Germany DrugEluting BalloonsMarket,Revenue ($m),2010-2017

Germany DrugEluting BalloonsMarket,Volume, 2003-2010

Germany DrugEluting BalloonsMarket,Volume, 2010-2017

France DrugEluting BalloonsMarket,Revenue ($m),2003-2010

France DrugEluting BalloonsMarket,Revenue ($m),2010-2017

France DrugEluting BalloonsMarket,Volume, 2003-2010

France DrugEluting BalloonsMarket,Volume, 2010-2017

Spain DrugEluting BalloonsMarket,Revenue ($m),2003-2010

Spain DrugEluting BalloonsMarket,Revenue ($m),2010-2017

Spain DrugEluting BalloonsMarket,Volume, 2003-2010

Spain DrugEluting BalloonsMarket,

market. Preliminary clinical trial results suggest that DEBs could become the standard treatment for PVD and complex lesions in the future. PACCOCATH ISR I and II showsignificant reductions in binary restenosis compared to balloon angioplasty. Another study showing the efficacy of DEB for SVD showed a binary restenosis rate of just5.5%. Market experts estimate that DEBs will account for more than 90% of all percutaneous interventions for PVD in the future.

B. Braun, Eurocor and Invatec Dominate Global Drug Eluting Balloons Market

Figure 2: Drug Eluting Balloons Market, Global, Key Company Share (%),

2010

Source: GlobalData, Annual Reports, SEC Filings, Investor Presentations, Earning CallTranscripts, News and Press Releases, Scientific Journals, Trade Associations, Interviewswith Industry Experts and Key Opinion Leaders (KOLs)

In 2010, B. Braun, Eurocor and Invatec were the three leading companies in the global DEB market and together accounted for 96% of the total market. B. Braun is themarket leader with a 60% market share, followed by Eurocor and Invatec (Medtronic) with 30% and 6% respectively. B. Braun’s product SeQuent Please currentlyaccounts for the highest number of completed and ongoing clinical trials. Bayer’s PACCOCATH technology has also been successfully demonstrated in animal models.Although Invatec has three approved products, it only entered the market in 2009. Lutonix, which received Conformité Européenne (CE) approval in 2011, is the newestplayer in the market. The size of the DEB market is expected to increase as products currently in clinical development get regulatory approval.

Introduction

Drug Eluting Balloons (DEBs) have recently come into the limelight following the Conformité Européenne (CE) approval of several DEB products and their subsequentlaunch in Europe. The recently concluded clinical trials in Europe have produced superior results over current interventions for a large number of indications such as In-Stent Restenosis (ISR), Peripheral Vascular Disease (PVD) and bifurcation lesions.

GlobalData Report Guidance

The report includes an executive summary capturing the key points in the global DEB market.

The third chapter describes the major cardiovascular indications for which DEBs are currently used. It discusses the disease overview, pathophysiology, risk factors anddisease etiology.

Chapter four deals with market characterization and details the features of the global DEB market size from 2007-2016. It also includes the key market drivers, restraintsand unmet need and an opportunity analysis.

Chapter five gives country-wise market information on the global DEB market, comprising eight regions: the UK, Germany, France, Spain, Italy, Australia, China and India.

Chapter six discusses the key market participants and competitive landscape of the DEBs market. It also includes profiles of key players in the market.

Chapter seven discusses the marketed DEB products with detailed product description and key technology and results of clinical trials.

Chapter eight also discusses market DEB products with detailed product description and key technology and results of clinical trials.

Chapter nine addresses and analyzes the current pipeline products by technology, unmet need and development stage. It also provides profiles of these products.

Chapter 10 discusses key Mergers and Acquisitions (M&A) along with partnerships in the DEB market are discussed in the last chapter. Some of the key deals that tookplace in 2008 and 2009 are discussed in detail.



Volume, 2010-2017

Italy DrugEluting BalloonsMarket,Revenue ($m),2003-2010

Italy DrugEluting BalloonsMarket,Revenue ($m),2010-2017

Italy DrugEluting BalloonsMarket,Volume, 2003-2010

Italy DrugEluting BalloonsMarket,Volume,2010-2017

The UK DrugEluting BalloonsMarket,Revenue ($m),2003-2010

The UK DrugEluting BalloonsMarket,Revenue ($m),2010-2017

The UK DrugEluting BalloonsMarket,Volume, 2003-2010

The UK DrugEluting BalloonsMarket,Volume, 2010-2017

Australia DrugEluting BalloonsMarket,Revenue ($m),2003-2010

Australia DrugEluting BalloonsMarket,Revenue ($m),2010-2017

Australia DrugEluting BalloonsMarket,Volume, 2003-2010

Australia DrugEluting BalloonsMarket,Volume,2010-2017

China DrugEluting BalloonsMarket,Revenue ($m),2003-2010

China DrugEluting BalloonsMarket,Revenue ($m),2010-2017

China DrugEluting BalloonsMarket,Volume, 2003-2010

China DrugEluting BalloonsMarket,Volume,

Major Cardiovascular Indications Approved for Drug Eluting Balloons

In-Stent Restenosis

Introduction

Restenosis takes place when a blood vessel is obstructed following Percutaneous Coronary Intervention (PCI) surgery, which can occur within six to nine months of theinitial procedure. Balloon angioplasty results in high rates of restenosis (25-50%) due to elastic recoil of the vessel and negative remodeling. Compared to balloonangioplasty, the risk of restenosis has been found to be up to 30-50% lower for Drug Eluting Stents (DES). Thus, more than 95% of PCI procedures currently use stents.However, restenosis can also occur with the use of stents, referred to as In-Stent Restenosis (ISR). It is usually defined during angiographic examination as a reduction inthe circumference of the lumen by 50% or more. The majority of patients require a second angioplasty within six months.

Pathophysiology

There are several reasons for the occurrence of ISR. In the majority of cases, fibrocellular growth within the blood vessel causes occlusion or blockage. The cause of thisblockage differs according to the type of PCI such as balloon angioplasty, Bare Metal Stents (BMS) or DES. ISR can produce symptoms that are very similar to those thatinitially prompted the patient to visit the interventional cardiologist, such as chest pain triggered by exertion.

Mechanisms of Action of In-Stent Restenosis

Elastic recoil: A reduction in the blood vessel lumen diameter resulting from a recoil occurring within seconds of balloon deflation and results in up to 40% loss of luminalarea. This problem is almost eliminated with the use of stents.

Neointimal hyperplasia: Neointimal hyperplasia is regarded as the main cause of ISR. This proliferative process is the arterial wall’s healing response to the acutemechanical injury provoked by stent deployment, such as injury of the endothelial cell lining, denudation and disruption of the lamina elastica.

Reorganization of thrombus: Angioplasty or stenting causes endothelial denudation and induces medial dissection. The consequent exposure of subintimal componentscauses platelet adherence and aggregation of blood resulting in thrombus formation. In DES, late to very late thrombosis (up to four years after the first procedure) hasbeen reported as causing restenosis. To prevent this, patients receive antiplatelet therapy for a few months following surgery.

All PCI procedures activate one or all of the above biological processes resulting in restenosis, which can be classified as procedural problems (nature of surgery andsurgical technique) and stent design.

Procedure Related Factors

Stent malapposition and Late Stent Malapposition (LSM): Occurs when a stent is not positioned flush to the interior arterial wall and pulls away or degrades, leaving aspace. It has been found to occur more frequently with DES than BMS and has been proposed as a cause of ISR.

Stent under-expansion and over-expansion: Stent under-expansion contributes to suboptimal final vessel geometry, resulting in inadequate drug delivery and non-inhibition of cell proliferation. Stent overexpansion can cause vessel overstretching and result in intimal injury, triggering neointimal proliferation or thrombus formation.

Incomplete lesion coverage: Causes restenosis at both ends of the stent.

Stent fracture: May lead to stent malapposition and vessel trauma.

Stent Related Factors

Asymmetric strut distribution: Results in non-homogenous drug delivery and consequent non-inhibition of cell proliferation.

Polymer disruption: May result in non-uniform local drug distribution leading to neointimal hyperplasia in non-treated regions.

Drug resistance: The vessel undergoes uninhibited smooth muscle cell proliferation due to insufficient drug inhibition.

Thrombus formation: Formation of blood clot on the stent can occlude the artery and may require revascularization.

Polymer or drug hypersensitivity: Triggers inflammatory reactions causing neointimal proliferation.

Etiology - Risk Factors

ISR does not occur in all patients uniformly and can be divided into patient-related and lesion-related factors.

Patient-Related Factors

Diabetes mellitus: Patients suffering from diabetes mellitus have increased incidence of restenosis. In a retrospective study from the Washington Hospital Center, therestenosis rate was found to be 16.3% for patients without diabetes, 17.6% for patients with type 2 diabetes, and 28% for patients with type 1 diabetes.

Polymorphisms: Individuals who carry the D allele of the Angiotensin-Converting Enzyme (ACE) or the polymorphism of glycoprotein IIIa are at increased risk of ISR.

C-Reactive protein: It has been shown that patients with restenosis at their six month angiographic follow-up have persistently elevated levels of C-reactive protein.

Recurrent restenosis: Patients who have previously suffered from at least one episode of stenosis are more likely to develop restenosis in the future.

Lesion-Related Factors

Lesion length: Restenosis risk has been found to be directly proportional to lesion length. Patients with lesions less than 15mm in length have a 27.9% restenosis rateversus 36.9% in patients with lesions greater than 15mm.



2010-2017

India DrugEluting BalloonsMarket,Revenue ($m),2003-2010

India DrugEluting BalloonsMarket,Revenue ($m),2010-2017

India DrugEluting BalloonsMarket,Volume, 2003-2010

India DrugEluting BalloonsMarket,Volume,2010-2017

Global Drug ElutingBalloons Market -Company ShareAnalysis and KeyMarketParticipants

Global DrugEluting BalloonsMarket,CompanyShare (%),2010

B. Braun

Global PTCACoronary DrugEluting Balloons -Key MarketedProducts

SeQuentPlease

DIORPaclitaxel-ElutingCoronaryBalloonCatheter

Elutax

Global PTA DrugEluting BalloonsMarket - KeyMarketed Products

Cotavance

IN.PACTPaclitaxelEluting BalloonCatheterSeries

FREEWAY 014

Global Drug ElutingBalloons Market -Strategic PipelineAssessment

PipelineTechnologyAssessment

Global Drug ElutingBalloons Market -Strategic DealsAnalysis

KeyAcquisitions

Appendix

Vessel size: Restenosis in vessels with a lumen diameter greater than ! 3mm have a restenosis rate of 19.9%, whereas lesions with a diameter less than 3mm haverestenosis rate of 32.6%.

Stent length: According to a study conducted at the Thorax Center in Rotterdam, the area of the stented segment versus stent length showed that the larger the area andthe shorter the stent deployed, the lower the restenosis rate.

Total occlusion: The risk of restenosis after the recanalization of a totally occluded vessel is higher than for a partially occluded vessel.

Saphenous vein grafts also lead to a higher risk of restenosis.

In-Stent Restenosis Epidemiology - Global

Treatment Flow Model

Figure 3: Treatment Flow Model, Drug Eluting Balloons for Treatment of In-Stent

Restenosis, Global, 2010

Source: GlobalData, WHO, heart.org Diseased Population refers to patients suffering from ISR

In-Stent Restenosis Prevalence

Over 1.1 million PCI are performed annually worldwide. Despite huge advances in devices, the biggest limitation is ISR, with approximately 25% of all patients sufferingfrom the disease. Patients with a high risk of restenosis such as diabetics, obese patients and patients suffering from total occlusion, saphenous vein bypass grafts andocclusion in small vessels have been observed as having a much higher ISR rate. More patients with multiple complications such as diabetes and obesity in patients aredeveloping Coronary Artery Disease (CAD), implying future growth in the number of patients with ISR. Moreover, ISR also varies according to stent type. BMS has beenshown to have ISR rates of up to 50% compared to 10% in DES after five years of stent implantation. Globally (EU5, Australia, China and India), approximately 275,000patients suffered from ISR in 2010.

In-Stent Restenosis Treatment Seeking Behavior

The treatment seeking rate for ISR is high because early restenosis in the case of BMS implants is easily detected during regular check-ups. It commonly manifests itselfin familiar symptoms such as chest pain or angina upon exertion. It may however go unnoticed by patients in the case of DES implants.

In-Stent Restenosis Diagnosis Rate

Diagnostic techniques such as stress tests and angiography are routinely used to detect restenosis and as such more than 95% of patients seeking treatment are correctlydiagnosed with the disease. In some countries, it is also routine practice to have an angiographic check-up six months after stent insertion, which accurately detectsmoderate to severe stenosis.

In-Stent Restenosis Prescription Rate

The largest patient leakage for treatment of ISR by DEB occurs at the prescription level, primarily due to the low rate of technology adoption by physicians. DEBs werelaunched in Europe in 2007 and in Asia-Pacific in 2009. Until now, there has been no clinical data to show the long term benefits of DEBs over conventional treatment



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methods such as DES or balloon angioplasty. Moreover, physicians tend to be skeptical of the data available, as clinical trials have only included patients with short lesionsrather than long lesions. Thus, only 15% of patients diagnosed with ISR are currently treated with DEB. However, in the future, this prescription rate is set to grow, giventhat early clinical trial results show a lower restenosis rate with DEB than with conventional Percutaneous Transluminal Coronary Angioplasty (PTCA) treatment. DEB canalso be used to avoid a second or a third layer of metal which reduces the flexibility of the vessel while delivering the drug uniformly.

Figure 4: Device Based Treatment Modalities for In-Stent Restenosis

Source: GlobalData

The success rate for the treatment of ISR varies depending on the type of interventional procedure used. No procedure is 100% effective and most are associated withsome degree of re-restenosis following revascularization. For BMS, the incidence of re-restenosis in coronary vessels ranges from 5-35% and is somewhat lower after theimplantation of a DES in patients who are at moderate risk. In high-risk patients, the rate of re-restenosis can be as high as 50-60% for BMS. The rates of re-restenosis inDES in BMS coronary vessels have been reported as 13-20% with the Cypher stent and 15-22% with the Taxus stent in clinical trials. However, these stent-in-stentapproaches involve two or more layers of metal in a native coronary artery. Uncoated or non-DEB catheters for coronary angioplasty are associated with one of thehighest rates of re-restenosis (40-70%). Rotation atherectomy or rotablation has been shown to give results similar to balloon angioplasty, and so is not preferred for ISR.Directional atherectomy has been shown to give better results with lower residual stenosis resulting in a lower angiographic re-restenosis rate of 30-50%. However, theintervention has proved popular for treating restenosis in peripheral vessels, as stenting procedures have been associated with strut fractures due to high stress. CuttingBalloon Angioplasty (CBA) has been shown to be more effective for ISR treatment than uncoated balloon angioplasty, with restenosis rates ranging from 12-30%. Intra-coronary irradiation (brachytherapy) has been found to be effective in this setting, with recurrence rates of 16-23%.

Compared to the aforementioned forms of treatment, DEB has shown much lower rates of Target Lesion Revascularization (TLR) at 6% versus stenting (15%) in a PEPCADII ISR study using B. Braun’s SeQuent Please DEB. This shows that DEB has a higher success rate than the currently available treatments. However, these results arerestricted to small lesions and no long term data is currently available.

Peripheral Vascular Disease - Overview and Pathophysiology

Introduction

PVD refers to atherosclerosis of the blood vessels (arteries and veins) located outside the heart and brain. The atherosclerosis of extremities causes ischemia. Mild PVDmay be asymptomatic or cause intermittent claudication (a painful, aching, cramping, uncomfortable or a tired feeling in the legs). Severe PVD may cause pain at rest,focal tissue necrosis and ischemic ulcers with skin atrophy, hair loss and cyanosis. The disease is age-related, and is generally observed in patients above the age of 50years. PVD prevalence also increases with age, and among the population of 70 years and above PVD prevalence is more than 10%. As atherosclerosis is a systemicdisorder, approximately 50-75% of patients with PVD also have clinically significant CAD or cerebrovascular disease. However, CAD may be asymptomatic because PVDprevents patients from sufficiently exerting themselves to trigger angina.

For the purpose of this report, PVD indications include diseases of small vessel below the knee, Small Vessel Disease (SVD) of peripheral arteries, femoral artery, renalartery and the femoropopliteal artery.

Pathophysiology

As with CAD, the most common cause of symptomatic obstruction in the peripheral arterial tree is atherosclerosis, a primarily systemic inflammatory process. In general,the lesion starts as fatty streaks. The resultant inflammatory process promotes cholesterol deposition and ultimately, the buildup of plaque. The lesions may be stable, ormay develop a thin, unstable fibrous cap that is vulnerable to ulceration. If the lesion ulcerates, the underlying plaque is exposed to the bloodstream and can causethrombotic occlusion or embolization.

Etiology - Risk Factors

The risk factors are the same as those for atherosclerosis:

High blood levels of bad Low-Density Lipoprotein (LDL) cholesterol and triglycerides and low blood levels of good High-Density Lipoprotein (HDL) cholesterol: The risk ofPVD increases by 5-10% with every 10mg/dL increase in total cholesterol levels. Levels of HDL below 40mg/dL and high triglyceride levels also increase the risk of PVD.

Smoking: Smoking increases the risk of PVD by up to 25 times. Approximately 80-90% of patients with PVD are current or former smokers. Progression to a more criticalstate of illness is likely for patients who continue to smoke after being diagnosed with PVD.

Diabetes mellitus (both type 1 and type 2 diabetes): People with type 2 diabetes are at three to four times the normal risk of developing PVD and intermittent claudication.People with type 2 diabetes also tend to develop more severe cases of PVD at an earlier age.



High blood pressure.

Chronic renal failure.

Obesity.

Physical inactivity.

High homocysteine level.

Genetic factors such as a family history of hypertension and atherosclerosis also put an individual at risk of developing PVD. Recent studies have shown that men have ahigher risk of PVD than women.

Peripheral Vascular Disease Epidemiology - Global

Treatment Flow Model

Figure 5: Treatment Flow Model, Drug Eluting Balloons for Treatment of Peripheral

Artery Disease, Global, 2010

GlobalData, WHO, heart.org Diseased Population refers to patients suffering from PVD

Peripheral Vascular Disease - Prevalence

PVD affects nearly 45 million people each year in Europe (the UK, Germany, France, Italy and Spain) and Asia (India, China and Australia) and 8-10 million in the US. PVDis common in adults above the age of 55 years, and has a prevalence rate of nearly 10%. The disease is age–related and so PVD is more prevalent in the older population.Males and the black population have also been found to be more at risk. With the growth of high risk populations such as diabetics, smokers and patients suffering fromhyperlipidemia and stress, PVD prevalence is expected to increase in the future. This fact, along with the poor overall outcome associated with unrecognized PVD, hasresulted in the recommendation of screening for PVD in all diabetic patients above 50 years by the American Diabetes Association.



Peripheral Vascular Disease - Treatment Seeking Behavior

The low treatment seeking rate for PVD is one of the leading causes of patient leakage. Asymptomatic and atypical presentation of the disease in approximately 30-40% ofpatients is the main reason for the low treatment seeking rate. One reason for the lack of symptoms is that in mild to moderate PVD, patients are not active enough totrigger leg ischemia and symptoms cease at rest. Another reason is atypical symptoms such as nonspecific exercise intolerance, hip or joint pain. In severe cases, ulcersusually appear after local trauma typically on the toes or heel and occasionally on the leg or foot. The ulcers tend to be painful, but people with peripheral neuropathy dueto diabetes or alcoholism may not feel them, which can also lead to delayed intervention.

Peripheral Vascular Disease - Diagnosis Rate

Clinical evaluation of PVD is generally inconclusive due to the absence or atypical symptoms. Non-invasive diagnostic techniques such as ankle-brachial Blood Pressure(BP) index and ultrasonography are routinely used to detect PVD and around 80% of patients seeking treatment are correctly diagnosed with the disease. However, forsurgical correction, angiography is a prerequisite in order to give details of the location and extent of arterial stenoses or occlusion.

Peripheral Vascular Disease - Prescription Rate

The largest patient leakage for the treatment of PVD by DEB occurs at the prescription level. The primary reason for this is the low percentage of surgically treatedpatients. The lack of appropriate surgical interventions that give long term results deters most physicians from using this line of treatment. Consequently, surgery is usedonly in severe cases where pain is persistent even on resting or the patient risks losing a limb to amputation in the future. Thus, less than 1% of the patients diagnosedwith PVD are currently treated with DEB. Being a new interventional device, the level of acceptance among doctors is very low. Most PVD cases are currently treatedthrough lifestyle changes and drug therapies such as antiplatelet treatment. Risk factor modification such as smoking cessation and diabetes control are crucial for thesepatients.

Peripheral Vascular Disease: Device Based Treatment Modalities and their Outcomes

Figure 6: Device Based Treatment Modalities for Peripheral Vascular Disease

Source: GlobalData

Treatment for PVD focuses on reducing symptoms and preventing further progression. In most mild to moderate cases, lifestyle changes, exercise and claudicationmedication are enough to slow progression or even reverse the symptoms of PVD. Medication to control high cholesterol levels and glucose in diabetics has also beenfound to be effective in most cases.

For a minority of patients, these recommendations and treatments are not sufficient and minimally invasive treatment or surgery is required. It is estimated that about25% of all patients suffering from claudication require revascularization. Minimally invasive procedures consist of angioplasty or stent placement or clot-removal treatment(brachytherapy). They are nonsurgical and are performed by making a small incision through which a catheter is inserted to reach the blocked artery. However, there iscurrently a substantial rate of recurrent restenosis of the artery at six months after angioplasty, which may occur in up to 30% of patients. Stenting with angioplastyreduces restenosis recurrence rates by half.

Endovascular brachytherapy, commonly used for occlusions in cases of superficial femoral artery, has good outcomes up to one year, but at five years up to 75% of thepatients require a second Percutaneous Transluminal Angioplasty (PTA) procedure. Endarterectomy is the preferred treatment for common femoral artery occlusions, buthas a high incidence of postoperative morbidity (15%). At one year after treatment, nearly 20% of patients experience some degree of restenosis.

Surgery for opening blocked blood vessels is necessary for severe symptoms and diffuse occlusions. A vein from another part of the body can be used to bypass andreroute blood around the closed artery. As PVD patients generally suffer from other complications such as hypertension, diabetes or hyperlipidemia, surgery carries a highrisk of mortality. Surgery has been shown to provide 75-95% five-year patency (state or quality of being open, expanded, or unblocked), which is comparable topercutaneous procedures for infrarenal aortic and iliac obstructive atherosclerotic disease.

Compared to the aforementioned treatments, DEB has shown much lower rates of TLR after 12 months at 15% versus PTA (48%) and PTA/local delivery of paclitaxel incontrast to local taxan injection in PACCOCATH-THUNDER (Local Taxan with sHort time contact for redUctioN of restenosis in Distal artERies) trials using B. Braun’s SeQuentPlease DEB. This shows that DEBs have a higher success rate than currently available treatments. However, these results are restricted to small lesions, and no long termdata is currently available.



Drug Eluting Balloons - Global Market Characterization

Global Drug Eluting Balloons Market, Revenue ($m), 2003-2010

Figure 7: Drug Eluting Balloons Market, Global, Revenue ($m), 2003-2010

Source: GlobalData, Annual Reports, SEC Filings, Investor Presentations, Earning Call Transcripts,News and Press Releases, Scientific Journals, Trade Associations, Interviews with Industry Expertsand Key Opinion Leaders (KOLs)

Table 1: Drug Eluting Balloons Market, Global, Revenue ($m), 2003-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010

PTCA Coronary DrugEluting Balloons

0.0 0.0 0.0 0.0 8.2 15.1 48.2 58.0 92%

PTA Peripheral DrugEluting Balloons

0.0 0.0 0.0 0.0 1.8 3.4 11.7 13.3 95%

Global Drug ElutingBalloons Market

0.0 0.0 0.0 0.0 10.0 18.5 59.9 71.3 93%

Source: GlobalData, Annual Reports, SEC Filings, Investor Presentations, Earning CallTranscripts, News and Press Releases, Scientific Journals, Trade Associations,Interviews with Industry Experts and Key Opinion Leaders (KOLs) Note: Numbershave been rounded off to the nearest decimal.

The global DEB market was valued at $71.3m in 2010 and has almost doubled each year since its launch in 2007. PTCA coronary DEBs are used for coronary heart diseaseindications such as ISR. The PTCA DEB market was valued at $58m in 2010 and grew at a Compound Annual Growth Rate (CAGR) of 92% in 2007–2010. The PTA DEBmarket was valued at $13.3m in 2010 and grew at a CAGR of 95% during the same period.

Global Drug Eluting Balloons Market, Revenue ($m), 2010-2017

Figure 8: Drug Eluting Balloons Market, Global, Revenue ($m), 2010-2017




Table 2: Drug Eluting Balloons Market, Global, Revenue ($m), 2010-

2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017

PTCA Drug ElutingBalloons

58.0 64 69 75 82 88 95 103 8.1%

PTA Drug ElutingBalloons

13.3 15 16 17 19 20 22 24 8.2%

Global Drug ElutingBalloons Market

71.2 78 85 93 100 108 117 127 8.1%

Source: GlobalData, Annual Reports, SEC Filings, Investor Presentations, Earning CallTranscripts, News and Press Releases, Scientific Journals, Trade Associations,Interviews with Industry Experts and Key Opinion Leaders (KOLs)

The DEB market is expected to grow at a CAGR of 8.1% to $127m in 2017. The PTCA DEB market is expected to grow at the same rate to $103m in 2017. The PTA DEBmarket is also expected to grow at the same rate to $24m in 2017.

The market is expected to be driven by an increased physician adoption rate as more authoritative clinical data is released and the device is adopted for new indicationssuch as PVD. The anticipated approval of DEB by the US Food and Drug Administration (FDA), in the next two to three years is also expected to boost DEB uptake in theUS. Moreover, because DEBs fulfill a huge unmet need gap in the market, adoption is expected to increase as physicians become aware of the product.

Global Drug Eluting Balloons Market, Volume (Units), 2007-2010

Figure 9: Drug Eluting Balloons Market, Global, Volume (Units), 2007-2010




Table 3: Drug Eluting Balloons Market, Global, Volume (Units), 2007-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010

PTCA CoronaryDrug ElutingBalloons

0 0 0 0 7,733 14,070 47,215 58,282 96.1%

PTA PeripheralDrug ElutingBalloons

0 0 0 0 1,718 3,208 11,237 13,349 98.1%

Global Drug ElutingBalloons Market 0 0 0 0 9,451 17,278 58,452 71,631 96.4%


A total of 71,631 units of DEBs were sold in 2010. The volume has increased at a CAGR of 96.4% in 2007-2010 due to new product launches in both PTCA and PTAcategories.

Global Drug Eluting Balloons Market, Volume (Units), 2010-2017

Figure 10: Drug Eluting Balloons Market, Global, Volume (Units), 2010-2017




Table 4: Drug Eluting Balloons Market, Global, Volume (Units), 2010-

2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017

PTCADrugElutingBalloons

58,282 65,859 73,922 82,742 92,291 102,629 113,918 127,311 11.0%

PTADrugElutingBalloons

13,349 15,045 16,858 18,827 20,953 23,244 25,743 28,690 11.3%

GlobalDrugElutingBalloonsMarket

71,631 80,904 90,780 101,569 113,244 125,873 139,661 156,001 11.3%


The volume of devices sold is expected to grow at a CAGR of 11.3% over the next seven years, driven by a rise in the number of procedures using DEBs. New productlaunches in the next few years are also expected to drive volume growth. In 2011, Lutonix launched its Moxy balloon catheter and announced its LEVANT 2 trials which willcontribute to gaining FDA approval.

Global Drug Eluting Balloons, Market Dynamics

Market Drivers

Potential for Providing a Better Treatment Option for a Number of Indications to Drive the Drug Eluting Balloons Market

The biggest opportunity for DEBs is their potential application in currently underserved indications, such as SR, bifurcation lesions, PVD and SVD, all of which are set tobenefit from DEB treatment.

Recent clinical studies suggest a much higher rate of patency with DEBs than other treatments for blocked arteries in a number of areas of the body. Other treatmentoptions include balloon angioplasty or stenting. Balloon angioplasty, one of the most popular treatments for PVD, has major drawbacks such as abrupt closure andrestenosis caused by elastic recoil, along with cellular proliferation and late remodeling. BMS was introduced after balloon catheters and solved the problem of vesseldissections and elastic recoil. They became the dominant mode of intervention but were fraught with problems such as stent thrombosis and increased neointimalhyperplasia and consequent ISR. DES was introduced in 2002 and uses anti-restenosis drugs to attenuate the healing and cellular processes after stenting, thus reducingthe need for repeat revascularization. However, late stent thrombosis, the dependence on prolonged Dual Antiplatelet Therapy (DAP) with DES and continued restenosis incomplex subset of lesions with DES give suboptimal results for these indications. Moreover, DES has limited use in peripheral artery occlusions such as superficial femoralarteries and popliteal arteries due to stent fractures in high torsion conditions.

Table 5: Drug Eluting Balloons Clinical Studies Showing Favorable

Results

Studies Objective Results

PACCOCATHISR I& II

The PACCOCATH ISR I andII studies aimed to test theefficacy and tolerance ofpaclitaxel-coated DEB forthe indication of coronaryISR.

The study results found that the DEBcatheter is effective in reducing LateLumen Loss (LLL) from 0.81 to 0.14mm inthe treatment of coronary ISR. Inaddition, the clinical data suggested areduction in the binary restenosis rate,and the need for TLR and in overall majorcardiac events upon using DEB.

PEPCAD II

The aim of PEPCAD I was toassess the safety andefficacy of SeQuent Pleasein the treatment of de novolesions in small vesselcoronary arteries with onlythe DEB.

Patients treated with SeQuent Pleasepresented with a binary restenosis rate ofonly 5.5% in vessels with an averagevessel diameter of less than 2.4mm.

LEVANT I

The objective of the study isto assess the safety andefficacy of the LutonixCatheter for the treatmentof stenosis of thefemoropopliteal arteries bydirect comparison tostandard balloon

The interim results of the trial showed thatthe Moxy balloon had the ability to safelyand substantially inhibit restenosis.



angioplasty.

THUNDER

The aim of the trial was totest the efficacy of localdelivery of paclitaxel toinhibit restenosis duringangioplasty of the leg.

Use of paclitaxel-coated balloon catheterssignificantly lowered the incidence ofrestenosis at six months and the rate oftarget-lesion revascularization at six, 12and 24 months. In contrast, the additionof paclitaxel to the angiographic contrastmedium did not have a significant effect.

INPACTDEEP

This is a prospective, multi-center, randomized trial ofsymptomatic patients withCritical Limb Ischemia)secondary to atheroscleroticlesions (stenotic oroccluded) of theinfrapopliteal vessels.

The preliminary results indicate adramatic reduction in the restenosis ratewith the application of the device. IN.PACTAmphirion reduced restenosis in CLIpatients with long lesions to 31% at threemonths compared to 69% with standardPTA balloon.


Preliminary clinical trial results suggest that DEBs could become the standard treatment for PVD and complex lesions in the future. For example, PACCOCATH ISR I and IIshow significant reductions in binary restenosis over balloon angioplasty. Another study, PEPCAD I, measuring the efficacy of DEB for SVD showed a binary restenosis rateof just 5.5%. Market experts estimate that DEB will account for more than 90% of all percutaneous interventions for peripheral vessel diseases in the future.

Advantages such as Higher Safety Profile and Lower Cost of Treatment for Drug Eluting Balloons to Drive Future Adoption

The shorter DAT regimen required by DEBs is expected to drive its adoption in the future. An elevated risk of thrombosis is present both shortly after PCI and during theperiod when stent struts are exposed to the circulation, prior to re-endothelialization. With the use of BMS, re-endothelialization occurs at one month after stentimplantation. Due to the risk of stent thrombosis with DES and BMS, all patients are prescribed antiplatelet therapy to prevent clot formation. The current guidelinesmandate DAT with aspirin and clopidogrel for at least 12 months after DES PCI or for as long as required. The use of aspirin often continues throughout the patient’slifetime. The drugs in DES (sirolimus and paclitaxel) reduce the risk of restenosis by inhibiting the proliferation of endothelial cells. However, this inhibition of normalhealing is associated with vessel-wall remodeling and sustained exposure of stent struts to the bloodstream for months or years after implantation, leading to late stentthrombosis three to five years after stent implantation.

Preliminary results show that the reduction of DAT to BMS protocol of three months appears safe. Thus, in elderly patients and pregnant women and patients with a highrisk of bleeding, DEBs are likely to become the preferred therapy as they require less antiplatelet therapy, in contrast to the 12 months required for DES.

Due to the reduced duration of antiplatelet therapy and the lower rate of revascularization, DEBs can create potential savings. For instance, if DEB is used in place of DESfor the treatment of ISR, the patient will only have to undergo antiplatelet therapy for three months, compared to 12 months for DES, saving the cost of nine months oftherapy. The rate of DEB revascularization is less than 10% while for DES it is almost 20%. These savings will also reduce the overall cost of intervention compared toDES. These cost advantages, along with easy access to the lesion in case of re-restenosis, are likely to drive DEB adoption in the future.

Growing Incidence of Complex Lesions and Peripheral Artery Disease to Boost Adoption in the Peripheral Vascular Devices Market

As DEB is a potential treatment for complex lesions and PVD, it is likely to increase its market penetration in the face of the growing population suffering from thesediseases. An estimated 20 million people in the US and Western Europe alone suffer from PVD leading to 250,000 amputations per year. The growing elderly population,increased rate of diabetes, smoking and the genetic predisposition to PVD in the global population is driving the rapid increase in the prevalence of the PVD.

Figure 11: Population Aged 65 and Over, Percentage (%), Global, 2010-2030



Source: GlobalData, Federal Interagency Forum on Aging-Related Statistics

Table 6: Population Aged 65 and Over, Percentage (%), Global, 2010-

2030

Year 2010 2030

% of Population Above 60 11% 17%

Source: GlobalData, Federal Interagency Forum on Aging-Related Statistics

The elderly population in developed markets such as Japan, Germany, Italy and France is increasing. The percentage of the global population above the age of 60 was11% in 2010 and is expected to grow to 17% by 2030. This is contributing towards increasing incidence rates of PVD because the risk of developing PVD increases withage.

The existence of co-morbidities such as CAD and diabetes greatly increases the risk of major cardiovascular events. A recent clinical study showed that patients withsymptomatic PVD alone had nearly one-third more major cardiovascular events than patients with CAD alone, and over 75% more than patients with cerebrovasculardisease alone. PVD as a single co-morbidity with CAD roughly doubles the risk of major cardiovascular events. Moreover, the prognosis for such patients is generally poor.Diabetes and smoking are also factors leading to a growth in the number of patients suffering from complex lesions such as bifurcations which are difficult to treat with DESdue to irregular anatomy. DEBs would be an ideal treatment for such lesions as they do not have these constraints.

Market Restraints

Limited Clinical Trial Results to Date have Resulted in Slow Adoption

DEB technology is very new and so there is widespread skepticism among physicians regarding its efficacy. The available clinical data employs fewer than 200 patients pertrial, and patients with long lesions have typically been excluded. Most clinical trials have yet to release long term outcome data. Thus, most physicians are adopting a ‘waitand watch’ stance regarding the technology and so companies are focusing only on physicians who are early technology adopters. This slow adoption is likely to continueto dampen the bottom line of companies until more reliable clinical data is released.

Few clinical trials have also reported inferior results in patients using DEBs compared to DES. This may prove to be a setback for adoption for few indications. Followingclinical trials have reported unfavorable results for DEBs.

Table 7: Drug Eluting Balloons Clinical Studies Showing Favorable

Results

Studies Objective Results

PEPCADIII

The aim of the study was toassess the safety andefficacy of the paclitaxel-eluting SeQuent Pleasefollowed by insertion of astent system (CoroflexDEBlue) in comparison tothe Sirolimus-elutingCypher stent in thetreatment of stenoses innative coronary arteries forprocedural success andpreservation of vesselpatency.

The results of this trial showed that the DEBand BMS treatment did not fare well againstthe Cypher stent system. Late in-stent lumenloss after the procedure was significantlygreater. Its associated TLR and Target VesselRevascularization (TVR) rates were found to bedouble compared to those of Cypher stenting.For paclitaxel eluting DEB/BMS the in-stent losswas found to be 0.44mm compared to 0.16mmin Cypher stent. In-stent late loss was found tobe 0.2mm in paclitaxel eluting DEB/BMScompared to 0.11mm in Cypher stent.

DEB-AMI

The aim of the study was tocompare results ofpaclitaxel-coated balloonsplus bare metal stents(BMS) with paclitaxel-eluting stents bare metalstents alone in patients withST-segment elevationmyocardial infarction.

The drug-eluting balloon group did not meetthe primary endpoint of reduced late lumenloss. Late lumen loss at six months was foundto be 0.64±0.56 in DEB and BMS, 0.78±0.59 inBMS and 0.21±0.32 for DES.




Lack of Reimbursement to Pose a Major Hurdle in Physician Adoption

As this is a new type of technology with limited clinical trial success, more research must be conducted in order to demonstrate its superiority over current standardsbefore it is reimbursed. Thus, adoption is likely to be slow in most cases. At present, DEBs cost upwards of $1,000, which is comparable to the cost of DES. However, asDES is reimbursed, hospitals will prefer to use DES over DEB wherever possible. This will limit the use of DEB to only those patients where DES cannot be used, such aselderly patients at high risk of bleeding, patients with a past history of stent fractures or those suffering from complex lesions.

Drug Eluting Balloons - Unmet Need and Opportunities

Figure 12: Unmet Need and Opportunities Analysis for Drug Eluting

Balloons

Source: GlobalData *PTA/PTCA: Percutaneous Transluminal Angioplasty/Percutaneous Transluminal Coronary Balloon Angioplasty

Unmet Need

Current interventions including DES give suboptimal results in a large number of indications and drug distributions.

ISR: DES intervention causes a double/triple metal layer in coronary arteries creating an imbalance between the unstented and stented portions of the vessel. Balloonangioplasty has poor outcomes with high revascularization rates.

Small vessels: DES has poor ‘crossability’. Balloon angioplasty has poor outcomes with high revascularization rates.

Bifurcation lesions: BMS and DES are cumbersome and result in an incomplete coverage of lesions as DES cannot fit into the Y-junction of bifurcation. Balloon angioplastyhas poor outcomes with high revascularization rates.

Below the knee lesions: Due to high torsion in the arteries below the knee, DES and BMS often suffer from strut fractures and kinking of unstented portions. Balloonangioplasty has poor outcomes with high revascularization rates.

Acute coronary syndrome: BMS and DES can cause problems due to LSM.

The long-term antiplatelet therapy required by DES creates safety issues with some sub-groups of patients.

DES causes uneven drug distribution as only a small part of the vessel is in contact with thin struts coated with the drug.

Opportunities



SVD, bifurcated lesions, ISR, and PVD represent a market worth nearly $2 billion. In addition, complications associated with long term antiplatelet therapy such as risk ofbleeding and contraindications limit the use of the current interventions. The associated cost and patient compliance issues also open the door for DEBs to enter thesemarkets. As DEBs can improve on both the safety and efficacy of the current treatments for some indications, they have the potential to create a niche in the PCI market.

Drug Eluting Balloons Market, by Country, Revenue ($m), Volume, 2003-2017

Germany Drug Eluting Balloons Market, Revenue ($m), 2003-2010

Figure 13: Drug Eluting Balloons Market, Germany, Revenue ($m), 2003-2010


Table 8: Drug Eluting Balloons Market, Germany, Revenue ($m), 2003-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010


0 0 0 0 2.57 4.09 14.90 16.61 86.3%


0 0 0 0 0.29 0.45 1.66 1.85 85.5%

Germany Drug ElutingBalloons Market

0 0 0 0 2.9 4.5 16.6 18.5 86.2%

Source: GlobalData, Annual Reports, SEC Filings, Investor Presentations, Earning CallTranscripts, News and Press Releases, Scientific Journals, Trade Associations,Interviews with Industry Experts and Key Opinion Leaders (KOLs) Note: The numbershave been rounded off to the nearest decimal

The DEB market in Germany was valued at $18.5m in 2010 and grew at a CAGR of 86.2% in 2007-2010. Germany’s market is the largest in the world and many DEBclinical trials are currently based there.

Germany Drug Eluting Balloons Market, Revenue ($m), 2010-2017

Figure 14: Drug Eluting Balloons Market, Germany, Revenue ($m), 2010-2017




Table 9: Drug Eluting Balloons Market, Germany, Revenue ($m), 2010–

2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


16.6 18.0 20.0 22.0 24.0 26.0 29.0 31.0 9.3%


1.9 2.0 2.0 2.0 3.0 3.0 3.0 3.0 7.2%

Germany Drug ElutingBalloons Market

18.5 20.0 22.0 24.0 27.0 29.0 32.0 34.0 9.1%


By 2017, Germany’s DEB market is expected to grow to $34m at a CAGR of 9.1% from 2010-2017. This growth will be due to growing clinical evidence of the advantagesof DEBs.

Germany Drug Eluting Balloons Market, Volume, 2003-2010

Figure 15: Drug Eluting Balloons Market, Germany, Volume (Absolute), 2003-2010




Table 10: Drug Eluting Balloons Market, Germany, Volume (Absolute),

2003-2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010


0 0 0 0 2,382 3,815 14,187 16,304 89.9%


0 0 0 0 265 424 1,576 1,812 89.8%

Germany DrugEluting BalloonsMarket

0 0 0 0 2,647 4,239 15,763 18,116 89.9%


18,116 units of DEBs were sold in 2010 in Germany alone. The market volume grew at a CAGR of 89.9% from 2007-2010.

Germany Drug Eluting Balloons Market, Volume, 2010-2017

Figure 16: Drug Eluting Balloons Market, Germany, Volume (Absolute), 2010-2017




Table 11: Drug Eluting Balloons Market, Germany, Volume (Absolute),

2010-2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017

PTCACoronaryDrug ElutingBalloons

16,304 18,636 21,129 23,882 26,878 30,098 33,671 38,096 12.9%

PTAPeripheralDrug ElutingBalloons

1,812 2,071 2,348 2,654 2,986 3,344 3,741 4,233 12.9%

GermanyDrug ElutingBalloonsMarket

18,116 20,707 23,477 26,536 29,864 33,442 37,412 42,329 12.9%


The DEB market volume in Germany is expected to increase to 42,329 by 2017, having grown at a CAGR of nearly 13%. Demand is expected to arise from both PTCA aswell as the PTA DEB market.

France Drug Eluting Balloons Market, Revenue ($m), 2003-2010

Figure 17: Drug Eluting Balloons Market, France, Revenue ($m), 2003-2010


Table 12: Drug Eluting Balloons Market, France, Revenue ($m), 2003-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010

PTCA Coronary DrugEluting Balloons - - - - 1.0 1.9 7.0 7.7 98.2%




- - - - 0.3 0.5 1.7 1.9 97.6%

France Drug ElutingBalloons Market

0 0 0 0 1.2 2.4 8.7 9.6 98.1%

Source: GlobalData

The French DEB market was valued at $9.6m in 2010 and grew at a CAGR of almost 100% from 2007-2010. The growth was primarily due to rapid adoption in the PTCADEB market.

France Drug Eluting Balloons Market, Revenue ($m), 2010-2017

Figure 18: Drug Eluting Balloons Market, France, Revenue ($m), 2010-2017


Table 13: Drug Eluting Balloons Market, France, Revenue ($m), 2010-

2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


7.7 8.5 9.2 9.9 10.6 11.3 11.9 12.9 7.6%


1.9 2.1 2.3 2.5 2.7 2.8 3.0 3.2 7.6%


9.6 10.6 11.5 12.4 13.2 14.1 14.9 16.1 7.6%


By 2017, the French DEB market is expected to reach $16.1m, having grown at a CAGR of 7.6% from 2010.

France Drug Eluting Balloons Market, Volume, 2003-2010

Figure 19: Drug Eluting Balloons Market, France, Volume (Absolute), 2003-2010




Table 14: Drug Eluting Balloons Market, France, Volume (Absolute),

2003-2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010


0 0 0 0 1,073 2,077 7,701 8,797 101.6%


0 0 0 0 268 519 1,925 2,199 101.7%


0 0 0 0 1,341 2,596 9,626 10,996 101.7%


Nearly 11,000 units of DEBs were sold in 2010. The market volume grew at a CAGR of 101.7% from 2007-2010.

France Drug Eluting Balloons Market, Volume, 2010-2017

Figure 20: Drug Eluting Balloons Market, France, Volume (Absolute), 2010-2017




Table 15: Drug Eluting Balloons Market, France, Volume (Absolute),

2010-2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


8,797 9,945 11,134 12,366 13,643 14,971 16,356 18,214 11.0%


2,199 2,486 2,783 3,091 3,411 3,743 4,089 4,554 11.0%

France DrugElutingBalloonsMarket

10,996 12,431 13,917 15,457 17,054 18,714 20,445 22,768 11.0%


By 2017, 22,768 units of DEBs are expected to have been been sold, with the market volume having grown at a CAGR of 11% from 2007-2010.

Spain Drug Eluting Balloons Market, Revenue ($m), 2003-2010

Figure 21: Drug Eluting Balloons Market, Spain, Revenue ($m), 2003-2010




Table 16: Drug Eluting Balloons Market, Spain, Revenue ($m), 2003-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010


- - - - 0.8 1.3 2.6 2.9 56.4%


- - - - 0.2 0.3 0.7 0.7 55.9%

Spain Drug ElutingBalloons Market

- - - - 0.9 1.7 3.2 3.6 56.3%


The Spanish DEB market was valued at $3.6m in 2010 and has grown at a CAGR of 56.3% since its launch in 2007. The slow growth compared to other European countrieswas due to the slow adoption rate among surgeons. Many clinical trials are ongoing and have yet to prove efficacious in the long term.

Spain Drug Eluting Balloons Market, Revenue ($m), 2010-2017

Figure 22: Drug Eluting Balloons Market, Spain, Revenue ($m), 2010-2017


Table 17: Drug Eluting Balloons Market, Spain, Revenue ($m), 2010-

2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


2.87 3.2 3.4 3.7 4.0 4.3 4.6 4.9 7.9%




0.72 0.8 0.9 0.9 1.0 1.1 1.1 1.2 7.6%


3.6 4.0 4.3 4.6 5.0 5.4 5.7 6.1 7.9%


Spain’s DEB market is expected to grow at a CAGR of nearly 8% to reach $6.1m in 2017.

Spain Drug Eluting Balloons Market, Volume, 2003-2010

Figure 23: Drug Eluting Balloons Market, Spain, Volume (Absolute), 2003-2010


Table 18: Drug Eluting Balloons Market, Spain, Volume (Absolute),

2003-2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010


0 0 0 0 703 1,262 2,481 2,835 59.2%


0 0 0 0 176 316 620 709 59.1%


- - - - 879 1,578 3,101 3,544 59.2%


Spain’s DEB market volume grew to 3,544 in 2010 at a CAGR of 59.2% from 2007-2010.

Spain Drug Eluting Balloons Market, Volume, 2010-2017

Figure 24: Drug Eluting Balloons Market, Spain, Volume (Absolute), 2010-2017




Table 19: Drug Eluting Balloons Market, Spain, Volume (Absolute),

2010-2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


2,835 3,215 3,605 4,022 4,460 4,912 5,400 6,035 11.4%


709 804 901 1,005 1,115 1,228 1,350 1,509 11.4%


3,544 4,019 4,506 5,027 5,575 6,140 6,750 7,544 11.4%


Spain’s DEB market volume is expected to grow to 7,544 by 2017, having grown at a CAGR of 11.4% from 2010-2017.

Italy Drug Eluting Balloons Market, Revenue ($m), 2003-2010

Figure 25: Drug Eluting Balloons Market, Italy, Revenue ($m), 2003-2010




Table 20: Drug Eluting Balloons Market, Italy, Revenue ($m), 2003-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010


- - - - 1.5 2.9 6.2 6.9 66.1%


- - - - 0.7 1.2 2.7 3.0 65.8%

Italy Drug ElutingBalloons Market

- - - - 2.2 4.1 8.8 9.9 66.0%


Italy’s DEB market was valued at $9.9m in 2010 and grew at a CAGR of 66% from 2007-2010. According to industry experts, DEBs have been well accepted amongcardiologists in Italy due to positive results and their potential to delay stenting procedures.

Italy Drug Eluting Balloons Market, Revenue ($m), 2010-2017

Figure 26: Drug Eluting Balloons Market, Italy, Revenue ($m), 2010-2017

Source: GlobalData, Annual Reports, SEC Filings, Investor Presentations, Earning Call Transcripts,News and Press Releases, Scientific Journals, Trade Associations, Interviews with Industry Experts



and Key Opinion Leaders (KOLs)

Table 21: Drug Eluting Balloons Market, Italy, Revenue ($m), 2010-

2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


6.9 8.0 9.0 9.0 10.0 11.0 12.0 13.0 9.4%


3.0 3.0 4.0 4.0 4.0 5.0 5.0 6.0 10.6%

Italy Drug ElutingBalloons Market

9.9 11.0 13.0 13.0 14.0 16.0 17.0 19.0 9.8%


Italy’s DEB market is expected to grow at a CAGR of 9.8% to reach $19m by 2017, driven by new product launches.

Italy Drug Eluting Balloons Market, Volume, 2003-2010

Figure 27: Drug Eluting Balloons Market, Italy, Volume (Absolute), 2003-2010


Table 22: Drug Eluting Balloons Market, Italy, Volume (Absolute), 2003-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010


0 0 0 0 1,500 2,891 6,356 7,324 69.6%


0 0 0 0 643 1,239 2,724 3,139 69.6%

Italy Drug Eluting



Balloons Market 0 0 0 0 2,143 4,130 9,080 10,463 69.6%


DEB market volume in Italy was 10,463 units in 2010 having grown at a CAGR of 69.6% from 2007-2010.

Italy Drug Eluting Balloons Market,Volume, 2010-2017

Figure 28: Drug Eluting Balloons Market, Italy, Volume (Absolute), 2010-2017


Table 23: Drug Eluting Balloons Market, Italy, Volume (Absolute), 2010-

2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


7,324 8,407 9,585 10,866 12,257 13,767 15,442 17,530 13.3%


3,139 3,603 4,108 4,657 5,253 5,900 6,618 7,513 13.3%

Italy DrugElutingBalloonsMarket

10,463 12,010 13,693 15,523 17,510 19,667 22,060 25,043 13.3%


Italy’s DEB market volume is expected to grow at a CAGR of 13.3% to reach 24,043 units in 2017, driven by new product launches.



The UK Drug Eluting Balloons Market, Revenue ($m), 2003-2010

Figure 29: Drug Eluting Balloons Market, The UK, Revenue ($m), 2003-2010


Table 24: Drug Eluting Balloons Market, The UK, Revenue ($m), 2003-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010


- - - - 1.7 3.2 7.6 8.4 71.5%


- - - - 0.3 0.6 1.3 1.5 72.6%

UK Drug ElutingBalloons Market

0 0 0 0 2.0 3.8 8.9 9.9 71.6%




Interviews with Industry Experts and Key Opinion Leaders (KOLs)

The UK’s DEB market was valued at $9.9m in 2010 having grown at a CAGR of 71.6% from 2007.

The UK Drug Eluting Balloons Market, Revenue ($m), 2010-2017

Figure 30: Drug Eluting Balloons Market, The UK , Revenue ($m), 2010-2017


Table 25: Drug Eluting Balloons Market, The UK, Revenue ($m), 2010-

2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


8.4 9.0 10.0 11.0 12.0 13.0 14.0 15.0 8.6%


1.5 2.0 2.0 2.0 2.0 2.0 2.0 3.0 10.5%

UK Drug ElutingBalloons Market

9.9 11.0 12.0 13.0 14.0 15.0 16.0 18.0 8.9%


The UK’s DEB market is expected to grow at a CAGR of 8.9% to reach $18m in 2017, driven by new product launches and growing physician adoption.

The UK Drug Eluting Balloons Market, Volume, 2003-2010

Figure 31: Drug Eluting Balloons Market, The UK, Volume (Absolute), 2003-2010




Table 26: Drug Eluting Balloons Market, The UK, Volume (Absolute),

2003-2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2007-2010


0 0 0 0 2,075 4,025 9,744 11,133 75.1%


0 0 0 0 366 710 1,719 1,965 75.1%

The UK Drug ElutingBalloons Market

0 0 0 0 2,441 4,735 11,463 13,098 75.1%


The UK’s DEB market volume was 13,098 in 2010 having grown at a CAGR of 75.1% from 2007.

The UK Drug Eluting Balloons Market, Volume, 2010-2017

Figure 32: Drug Eluting Balloons Market, The UK, Volume (Absolute), 2010-2017




Table 27: Drug Eluting Balloons Market, The UK, Volume (Absolute),

2010-2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


11,133 12,613 14,192 15,946 17,888 20,027 22,361 25,178 12.1%


1,965 2,226 2,505 2,814 3,157 3,534 3,946 4,443 12.1%

The UK DrugElutingBalloonsMarket

13,098 14,839 16,697 18,760 21,045 23,561 26,307 29,621 12.1%


The DEB market volume is expected to grow at a CAGR of 12.1% to reach 29,621 units by 2017.

Australia Drug Eluting Balloons Market, Revenue ($m), 2003-2010

Figure 33: Drug Eluting Balloons Market, Australia, Revenue ($m), 2003-2010




Table 28: Drug Eluting Balloons Market, Australia, Revenue ($m), 2003-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2009-2010


- - - - - - 1.7 1.9 12%


- - - - - - 0.4 0.5 12%

Australia Drug ElutingBalloons Market

- 0.0 0.0 0.0 0.0 0.0 2.1 2.3 12%


The Australian DEB market was valued at $2.3m in 2010, having only been introduced in 2009.

Australia Drug Eluting Balloons Market, Revenue ($m), 2010-2017

Figure 34: Drug Eluting Balloons Market, Australia, Revenue ($m), 2010-2017


Table 29: Drug Eluting Balloons Market, Australia, Revenue ($m), 2010-

2017

2003 2004 2005 2006 2007 2008 2009 2010CAGR2009-2010


- - - - - - 1.7 1.9 12%


- - - - - - 0.4 0.5 12%


- 0.0 0.0 0.0 0.0 0.0 2.1 2.3 12%

Source: GlobalData, Annual Reports, SEC Filings, Investor Presentations, Earning CallTranscripts, News and Press Releases, Scientific Journals, Trade Associations,



Transcripts, News and Press Releases, Scientific Journals, Trade Associations,Interviews with Industry Experts and Key Opinion Leaders (KOLs)

The Australian DEB market is expected to grow at a CAGR of 12% to reach $2.3m by 2017.

Australia Drug Eluting Balloons Market, Volume, 2003-2010

Figure 35: Drug Eluting Balloons Market, Australia, Volume (Absolute), 2003-2010


Table 30: Drug Eluting Balloons Market, Australia, Volume (Absolute),

2003-2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2009-2010


- - - - - - 1,628 1,881 12%


- - - - - - 407 470 12%


- 0.0 0.0 0.0 0.0 0.0 2,035 2,351 12%


The Australian DEB market volume was 2,351 in 2010 and the CAGR for 2009-2010 was 12%.

Australia Drug Eluting Balloons Market,Volume, 2010-2017

Figure 36: Drug Eluting Balloons Market, Australia, Volume (Absolute), 2010-2017




Table 31: Drug Eluting Balloons Market, Australia, Volume (Absolute),

2010-2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


1,881 2,165 2,466 2,802 3,170 3,559 3,995 4,542 14%


470 541 616 701 792 890 999 1,135 14%

Australia DrugEluting BalloonsMarket

2,351 2,706 3,082 3,503 3,962 4,449 4,994 5,677 14%

Source: GlobalData, Annual Reports, SEC Filings, Investor Presentations, Earning CallTranscripts, News and Press Releases, Scientific Journals, Trade Associations,

Interviews with Industry Experts and Key Opinion Leaders (KOLs)

The Australian DEB market volume is expected to grow to 5,677 by 2017, having grown at a CAGR of 14% from 2010.

China Drug Eluting Balloons Market, Revenue ($m), 2003-2010

Figure 37: Drug Eluting Balloons Market, China, Revenue ($m), 2003-2010




Table 32: Drug Eluting Balloons Market, China, Revenue ($m), 2003-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2009-2010


- - - - - - 5.7 6.3 11%


- - - - - - 0.3 0.3 10%

China Drug ElutingBalloons Market

- - - - - - 6.0 6.6 11%


The Chinese DEB market was valued at $6.6m in 2010, having grown at a CAGR of 11% after being introduced in 2009.

China Drug Eluting Balloons Market, Revenue ($m), 2010-2017

Figure 38: Drug Eluting Balloons Market, China, Revenue ($m), 2010-2017






2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


6.3 7.0 8.0 8.0 9.0 10.0 11.0 12.0 9%


0.3 0.4 0.4 0.4 0.5 0.5 0.6 0.6 9%


6.6 7.4 8.4 8.4 9.5 10.5 11.6 12.6 9%


The Chinese DEB market is expected to grow at a CAGR of 9% to reach $12.6m in 2017. The cost effectiveness of DEBs over DES is expected to drive growth in China.

China Drug Eluting Balloons Market, Volume, 2003-2010

Figure 39: Drug Eluting Balloons Market, China, Volume (Absolute), 2003-2010


Table 34: Drug Eluting Balloons Market, China, Volume (Absolute),

2003-2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2009-2010


0 0 0 0 0 0 3,868 4,407 14%


0 0 0 0 0 0 204 232 14%


- - - - - - 4,072 4,639 14%




The Chinese DEB market volume was 4,639 in 2010 having grown at 14% in 2009-2010.

China Drug Eluting Balloons Market,Volume, 2010-2017

Figure 40: Drug Eluting Balloons Market, China, Volume (Absolute), 2010-2017


Table 35: Drug Eluting Balloons Market, China, Volume (Absolute),

2010-2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


4,407 5,016 5,673 6,426 7,251 8,220 9,270 10,503 13%

PTA PeripheralDrug ElutingBalloons

232 264 299 338 382 433 488 553 13%

China Drug Eluting

Balloons Market 4,639 5,280 5,972 6,764 7,633 8,653 9,758 11,056 13%


The Chinese DEB market volume is expected to grow at a CAGR of 13% to reach 11,056 in 2017.

India Drug Eluting Balloons Market, Revenue ($m), 2003-2010

Figure 41: Drug Eluting Balloons Market, India, Revenue ($m), 2003-2010




Table 36: Drug Eluting Balloons Market, India, Revenue ($m), 2003-

2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR2009-2010


0 0 0 0 0 0 1.3 2.1 50%


0 0 0 0 0 0 0.1 0.2 50%

India Drug ElutingBalloons Market - - - - - - 1.4 2.3 50%


India’s DEB market was valued at $2.3m in 2010 after having been launched in 2009.

India Drug Eluting Balloons Market, Revenue ($m), 2010-2017

Figure 42: Drug Eluting Balloons Market, India, Revenue ($m), 2010-2017




Table 37: Drug Eluting Balloons Market, India, Revenue ($m), 2010-

2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


2.1 2.2 2.3 2.4 2.4 2.5 2.6 2.7 3%


0.2 0.2 0.3 0.3 0.3 0.3 0.3 0.4 9%

India Drug ElutingBalloons Market 2.3 2.4 2.5 2.6 2.7 2.9 3.0 3.1 4%


India’s DEB market is expected to grow at a CAGR of 4% to reach $3.1m as the Indian medical devices market is typically slow to adopt new technology. DEBs arecurrently undergoing trials and long term efficacy is still being investigated.

India Drug Eluting Balloons Market, Volume, 2003-2010

Figure 43: Drug Eluting Balloons Market, India, Volume (Absolute), 2003-2010


Table 38: Drug Eluting Balloons Market, India, Volume (Absolute),

2003-2010

2003 2004 2005 2006 2007 2008 2009 2010CAGR



2003 2004 2005 2006 2007 2008 2009 2010CAGR2009-2010


0 0 0 0 0 0 1,250 1,850 48%


0 0 0 0 0 0 134 188 40%

India Drug ElutingBalloons Market

- - - - - - 1,384 2,038 47%


The Indian DEB market volume was nearly 2,000 units in 2010, having grown at a CAGR of 47% from 2009.

India Drug Eluting Balloons Market,Volume, 2010-2017

Figure 44: Drug Eluting Balloons Market, India, Volume (Absolute), 2010-2017


Table 39: Drug Eluting Balloons Market, India, Volume (Absolute),

2010-2017

2010 2011 2012 2013 2014 2015 2016 2017CAGR2010-2017


1,850 1,924 2,001 2,081 2,164 2,251 2,341 2,435 4%


188 204 221 240 261 283 307 333 8%

India Drug ElutingBalloons Market

2,038 2,128 2,222 2,321 2,425 2,534 2,648 2,768 5%




The Indian DEB market volume is expected to rise to 2,768 by 2017 driven by improved clinical data and cost effectiveness.

Global Drug Eluting Balloons Market - Company Share Analysis and Key Market Participants

Global Drug Eluting Balloons Market, Company Share (%), 2010

Figure 45: Drug Eluting Balloons Market, Global, Company Share (%),

2010


Table 40: Drug Eluting Balloons Market, Global, Key Company Shares

(%), 2010

2010 Revenue ($m)

B. Braun 42.7

Eurocor 21.4

Invatec 4.3

Others 2.8

Source: GlobalData, Annual Reports, SEC Filings, Investor Presentations, Earning CallTranscripts, News and Press Releases, Scientific Journals, Trade Associations,Interviews with Industry Experts and Key Opinion Leaders (KOLs) Note: Numbershave been rounded off to the nearest decimal point.

In 2010, B. Braun, Eurocor and Invatec were the leading companies in the global DEB market and together accounted for 96% of the total market. B. Braun is the marketleader with a 60% share, followed by Eurocor and Invatec (Medtronic) with 30% and 6% respectively. B. Braun’s product SeQuent Please currently has the highest numberof completed and ongoing clinical trials. Bayer’s PACCOCATH technology has also been successfully demonstrated in animal models. Invatec has three approved products,despite only entering the market in 2009.

B. Braun

Overview

B. Braun Melsungen AG (B. Braun) is a global healthcare company involved in marketing and selling products and services catering to the basic healthcare, intensive careunits, anesthesia and emergency care sectors. The company also provides solutions for extracorporeal blood treatment and surgical core procedures. It operatesworldwide, principally in Europe, Switzerland, the US, Brazil and Malaysia. The company is headquartered in Melsungen, Germany.



The company’s aesculap division has become a system provider for the complete core process in the operating theatre by offering system solutions ranging from surgicalaccess, to the surgery itself to wound closure and sterile reprocessing. Products include surgical instruments for open or minimally invasive surgery, implants, surgicalsutures, sterile containers, storage, motor and navigation systems and cardiology products. The business areas of this division are Surgical Technologies/Sterile ContainerSystems, Closure Technologies, Orthopaedics, Spine, Neurosurgery, Power Systems and Vascular Systems.

Drug Eluting Balloons Portfolio

Marketed Products

B. Braun currently has only one marketed product, namely SeQuent Please. It is involved in a large number of clinical trials to test the efficacy of the device for indicationssuch as ISR, SVD and PVD.

Pipeline Products

Table 41: B. Braun, Drug Eluting Balloons, Pipeline Products

Product Name Indication Territory

SeQuentPlease

ISR, SVD, PVD, bifurcations, de novo lesions and stentthrombosis

The US

Source: GlobalData, Company Websites, News and Press Releases

This product is currently awaiting FDA approval.

Eurocor

Overview

Eurocor GmbH (Eurocor) is engaged in the development and manufacturing of interventional cardiology products. The company was acquired by Opto Circuits (India) Ltd.in 2006. In 2009, the company launched its DIOR DEB in the Asian markets of India, Singapore, Indonesia and Vietnam. The company also entered into a strategicagreement with US-based coating company, Micell Technologies to develop new balloon and stent systems for the global market. The company reported revenues of INR1,037.7m in 2008-2009. It is headquartered in Bonn, Germany.

Its product portfolio includes the Genius TAXCOR coronary stent system, the MEGAFLEX coronary stent system, the Genius MAGIC coronary stent system, the AMADEUSSUPERCROSS coronary dilatation catheter and the Radimax peripheral stent system, which are utilized for the treatment of CAD and VAD. It also develops fullybiodegradable coronary stent implants. The company's products are sold through a network of international distributors across Japan, Belgium, Israel and other foreigncountries. The company is headquartered in Bonn, Germany.

Marketed Products

The company currently markets DIOR across Europe and Asia. It was one of the first companies to get obtain CE approval for DEBs. Since 2009, the company launchedtwo more products in the DEB segment outside the US:

Magical: Eurocor’s CE-marked novel drug-eluting option that combines a BMS with a DEB for rapid healing without the need for long-term anti-platelet therapy.

Freeway: A paclitaxel eluting balloon dilatation catheter which is expected to be a primary option for interventionists treating diabetic and atherosclerotic patients withperipheral artery blockages.

Pipeline Products

Table 42: Eurocor, Drug Eluting Balloons, Pipeline Products


DIOR Paclitaxel-Eluting CoronaryBalloon Catheter

ISR, SVD The US

FREEWAY Paclitaxel-ElutingPeripheral Balloon Catheter

PVD (superficial femoral artery,below the knee artery)

The US


Eurocor’s FREEWAY paclitaxel-eluting peripheral balloon catheter and DIOR are currently undergoing clinical trials in the US and awaiting FDA approval.

Invatec

Overview

Invatec S.p.A. (Invatec) is a medical device company engaged in developing, manufacturing, marketing and selling vascular stents and minimally invasive radiofrequencyablation technology products in the interventional vascular field. The company provides products in four categories, namely coronary, supraaortic, peripheral and



radiofrequency. Invatec distributes its products in Europe, the Middle East, Africa, the Americas, the Far East and Asia-Pacific through a wide network of distributors. It isheadquartered in Roncadelle, Italy.

Its product range includes self-expanding stent systems, multi-purpose angioplasty support catheters, peripheral self-expanding stent systems, guidewires, balloon-expandable stents, RX PTA balloon catheters, PTCA balloon catheters, PTCA bifurcation balloon catheters, PTCA balloon catheters, rapid exchange type high pressureballoons, proximal flow blockage cerebral protection devices, clot extraction catheters, coronary stent systems, infrapopliteal balloon-expandable stent systems and renalRX stent systems.

In 2010 the company received 510(k) clearance from the FDA to market REEF HP, a PTA balloon catheter for use in peripheral high pressure dilatation procedures.


Marketed Products

The company currently markets three CE-approved DEBs. In January 2009, Invatec launched the IN.PACT Amphirion drug-eluting catheter, designed specifically to treatatherosclerosis in arteries located below the knee. In March 2009, it received approval for the IN.PACT Falcon, paclitaxel-eluting PTCA balloon catheter, which was the firstDEB intended to treat atherosclerosis in the coronary arteries. The IN.PACT Falcon is expected to have immediate application in treating ISR in coronary arteries. In May2009, another Invatec DEB received CE approval, designed specifically for PVD. With this launch, Invatec became the only company in the world to market a DEB on threedifferent balloon platforms targeting three different areas: the coronary vessels, the vessels below the knee and the vessels above the knee.

Pipeline Products

Table 43: Invatec, Drug Eluting Balloons, Pipeline Products


IN.PACT Admiral DEBPVD (Superficial FemoralArtery)

The US

IN.PACT Amphirion Paclitaxel Eluting BalloonCatheter

Below the Knee Artery The US

IN.PACT Falcon PTCA Balloon Catheter Coronary Artery The US

IN.PACT Pacific Balloon CatheterPVD (Superficial FemoralArtery)

Global


The company is currently awaiting FDA approval for four of its products. IN.PACT Pacific has not yet received CE or FDA approval.

Aachen Resonance GmbH

Overview

Aachen Resonance GmbH (Aachen Resonance) is engaged in the development and manufacturing of stents and PTCA catheters. The company is a pioneer in the field ofinvasive cardiology, providing a wide range of treatment possibilities with drug eluting devices for several applications. It currently holds a number of international patentsfocused on intravascular stenting, balloon production and coating technologies. The company is headquartered in Aachen, Germany.

The company maintains strong relationships with universities, medical centers of clinical and scientific relevance and technical research centers. Through these scientificpartnerships, Aachen Resonance continues to develop new devices such as VITA Stent, a DES coated with tretinoin; and ELUTAX, a DEB coated with paclitaxel.

Recently, Aachen Resonance received a CE mark for its ARTAX coronary drug eluting stent coated with paclitaxel, a VITA coronary drug eluting stent coated with Tretinoinand the ELUTAX PTCA catheter coated with paclitaxel.


Marketed Products

The company’s marketed product Elutax has been recently given CE approval. The company utilizes a unique drug coating technology of pure paclitaxel and claims toensure almost 100% drug delivery to the vessel walls.

Pipeline Products

Table 44: Aachen Resonance, Drug Eluting Balloons, Pipeline Products


ELUTAX Coronary Vessel Disease, SVD The US


Global PTCA Coronary Drug Eluting Balloons - Key Marketed Products



SeQuent Please

Product Overview and Description

SeQuent Please is a DEB catheter developed by B. Braun that delivers anti-restenosis drug paclitaxel directly to the lesion during angioplasty. In 2009, the companyobtained CE mark certification for the product, and it is currently available in most European and Asian countries. It is intended to be used for all common coronary lesions,and has concluded clinical trials for the following indications:

Patients with ISR.

SVD for coronary arteries with diameters of up to 2.8mm.

Bifurcation lesions.

The DEB system enables the delivery of a large dose of the drug to the lesion for a short time. This strategy has been proven beneficial in in vitro studies by preventingneointimal proliferation. The balloon surface of the SeQuent Please DEB system is coated with a dispersion of paclitaxel with a dose of 3µg/mm2 and Ultravist 370(iopromide). Iopromide is a well tolerated non-ionic X-ray contrast agent which is used as a spacer in the DEB system. Thus, the device enables polymer-free delivery tothe lesions due to the unique matrix technology used for coating drugs. Unlike DES, the absence of a polymer to coat the drug is said to reduce the incidence of latethrombosis.

Paclitaxel is released during balloon expansion directly at the location of the stenosis during 30-60 second contact between the balloon surface and the vessel wall.

Key Technology

SeQuent Please uses the proprietary matrix technology PACCOCATH, which provides a unique matrix of paclitaxel and a hydrophilic spacer on the surface of the balloon.The matrix comprises the anti-restenosis drug paclitaxel and the radiological contrast agent Ultravist 370. This creates a large contact surface area between the lipophilicdrug and the vessel wall, as well as a high bioavailability of paclitaxel at the target site for rapid drug absorption. This allows the uniform and complete application of thedrug after the first balloon inflation. After the inflation, the matrix dissolves immediately so that no material is left behind that could potentially lead to complications.

Bayer Schering Pharma AG is the owner of the PACCOCATH trademark and technology and is developing it for market through the Bayer affiliate, MEDRAD Inc. under thebrand name Cotavance. B. Braun and MEDRAD recently signed a co-marketing and trademark licensing agreement.

Past Clinical Studies

Some randomized, multi-center trials on the safety and efficacy of the SeQuent Please technology for the treatment of coronary ISR, PVD and SVD have been completed.Two trials for ISR were double blinded (PACCOCATH ISR I and ISR II) and randomized to uncoated balloons, whereas in one trial (PEPCAD II) a blinding procedure was notpossible due to the nature of the control group device (TAXUS Liberté). Results have also been released for the THUNDER and PACCOCATH FEM trials which explore thedevice applications in PVD. Most studies show positive results in lowering restenosis and adverse events rate upon the use of the SeQuent Please.

There are also several trials which compare the efficacy of DEB followed by implantation of a BMS versus implantation of a drug eluting stent. PEPCAD III, one of theearliest studies which compared paclitaxel eluting balloon Sequent Please with sirolimus eluting Cypher showed disappointing results. Results for studies which compareTaxus Liberté, Taxus and Xience V with DEB have not yet been released.

PEPCAD V

The aim of the study was to investigate the feasibility of paclitaxel-eluting PTCA-balloon dilation (SeQuent Please followed by BMS (Coroflex) deployment for the treatmentof significant de-novo bifurcation stenoses in the native left coronary artery and evaluate the preservation of vessel patency. Target group size for the study wasdetermined to be 25.

Patients with single or multiple coronary artery disease were included. The DEB was be deployed in the main branch of bifurcation stenoses. Diameter stenosis before theprocedure must be either more then 70% in either one or both branches of the lesion (bifurcational lesion of any type of the Medina classification) or more than 50% ifischemia corresponding to the target lesion is documented either by exercise stress Electrocardiogram (ECG), stress echocardiography, scintigraphy, MRT or suspectedbased on angina pectoris The reference diameter was defined as 2.5-3.8mm, while reference diameter of side branch must be 2.0-3.5mm. The length of stenoses in eitherbranch was defined as 20mm. The primary end point was defined as LLL at nine months with a deviation allowance of +/- three months.

The results of the study are yet to be released.

PEPCAD IV

The objective of the study is to compare the efficacy of procedural success and preservation of vessel patency of paclitaxel-eluting PTCA-balloon dilation (SeQuent Please)followed by insertion of cobalt-chromium stent (Coroflex Blue) deployment to treatment with -eluting stent (Taxus Liberté). This study is a prospective, randomized, multi-center, two-armed phase-II pilot study conducted in Malaysia and Thailand. 128 diabetes mellitus patients are expected to be recruited to either of the treatment groupswith 20 to 50 patients assigned per center.

The efficiency is being studied for the treatment of de novo stenoses in native coronary arteries. The reference diameter indicated for the study is > 2.5mm and < 3.5mm.The length of stenosis considered is between 10mm and 20mm. Patients who have had diabetes mellitus for three years treated orally or through subcutaneously havealso been considered for the study. Other patient inclusions include patients with stable blood glucose for six months, stable angina pectoris and patients eligible forcoronary revascularization by PCI. Primary end points include LLL at nine months.

The results of the study have not yet been published.

PEPCAD III

The aim of the study was to assess the safety and efficacy of the paclitaxel-eluting SeQuent Please followed by insertion of a stent system (Coroflex DEBlue) in comparisonto the Sirolimus-eluting Cypher stent in the treatment of stenoses in native coronary arteries for procedural success and preservation of vessel patency. This study is aprospective, randomized, multi-center, two-armed Phase II study conducted in Europe in six countries. It was the first major study for DEB/BMS systems.



600 patients were randomly assigned to a treatment group in the order of 20 to 40 patients per centre and a minimum of 10 procedures per operator. Patients with stableor selected forms of unstable angina or documented ischemia due to a significant lesion in a native coronary artery were included. Patients whose vessels may not supplyan entirely infarcted myocardial area were also included. LLL at nine months with a deviation of +/- three months was the primary end point.

Clinical and angiographic follow-up was scheduled at nine months for all patients with one and three year follow up for Major Adverse Cardiac Events (MACE) for allpatients.

The results of this trial showed that the DEB and BMS treatment did not fare well against the Cypher stent system. Late in-stent lumen loss after the procedure wassignificantly greater. Its associated TLR and Target Vessel Revascularization (TVR) rates were found to be double compared to those of Cypher stenting. For paclitaxeleluting DEB/BMS the in-stent loss was found to be 0.44mm compared to 0.16mm in Cypher stent. In-stent late loss was found to be 0.2mm in paclitaxel eluting DEB/BMScompared to 0.11mm in Cypher stent.

PEPCAD DES

The aim of the study is to assess the efficacy of the paclitaxel-eluting PTCA balloon catheter SeQuent Please in treating ISR of various DES in native coronary arteries withreference diameters between 2.5mm and = 3.5mm and lesion lengths < or = 22mm. The use of DES to treat ISR lowered restenosis is in the single digit range. Recently,the use of matrix coated paclitaxel-eluting PTCA balloon catheters (SeQuent Please, Paccocath Technology, Bayer/Schering & B. Braun Melsungen AG) was compared toPES in the PEPCAD II trial which showed significantly lower six month LLL, six month MACE and TVR rates for SeQuent Please (7.25%) compared to PES for which the 12month TVR rate was 19.0% and therefore in agreement with prior studies (ISAR DESIRE). As these assessments were conducted in patients with BMS ISR, it is crucial tostudy ISR of failed DES implantations as they may cause continued chronic inflammatory responses caused by the non-bioabsorbable polymer in particular once the drugrelease has ceased. A total of 120 patients were to be enrolled for this study. The primary end point for the study is LLL.

The trial results have yet to be released.

PACCOCATH ISR I and II

The PACCOCATH ISR I and II studies aimed to test the efficacy and tolerance of paclitaxel-coated DEB for the indication of coronary ISR. The PACCOCATH ISR studieswere randomized, double-blinded, placebo-controlled, multicenter trials and 108 patients (ISR-I n = 52; ISR-II n = 56) were recruited. The patients were randomized torepeat PTCA of ISR either using the DEB catheter or an uncoated PTCA catheter of the same type, forming the control group.

Patients suffering from ISR in a coronary artery with a stenosis diameter of at least 70%, a stented segment length of < 25mm (ISR-I) or < 30mm (ISR-II), and a vesseldiameter of at least 2.5mm and up to 3.5mm were the major inclusion criteria. The primary endpoint was LLL after six months, which was determined by an independent,blinded angiographic core lab. Secondary endpoints included the binary restenosis rate (% of patients with >50 % diameter stenosis at control angiography) and MACE,defined as vessel closure/thrombosis, TLR, myocardial infarction, stroke and death.

The study results found that DEB catheter is effective in reducing LLL from 0.81 to 0.14mm in treatment of coronary ISR. In addition, the clinical data suggested areduction in the binary restenosis rate, the need for TLR and in overall major cardiac events upon using DEB. Thus, the need for fewer interventions to treat stenoticcoronary segments presents a significant patient benefit and may further reduce health care costs relative to the interventions and associated co-medication.

PEPCAD I

The aim of PEPCAD I was to assess the safety and efficacy of SeQuent Please in the treatment of de novo lesions in small vessel coronary arteries with only DEB. 118patients were evaluated in the study, of which 82 patients were treated solely with the DEB system.

In the PEPCAD I trial, patients with reference diameters of > 2.25mm and < 2.8mm and < 22mm in length were included. In case of vessel recoil or dissection, theadditional implantation of a BMS was allowed. In the present trial, after drug-coated balloon angioplasty 28% of the patients underwent BMS implantation due to acuteelastic recoil or severe dissections. In this study, LLL and binary restenosis rates were the endpoints and show similar results to recently published data on DES in coronarySVD.

Patients treated with the SeQuent Please presented a binary restenosis rate of only 5.5% in vessels with an average vessel diameter of less than 2.4mm. In this patientsubset, binary restenosis rates of 20% to 31% have been reported for DES. Earlier trials in coronary artery SVD reported cross-over rates to additional stent implantationin the angioplasty groups from 16-40%. High incidences of geographical mismatch in patients with the additional implantation of a BMS after pre-treatment with the DEBwere observed in this study. The observed restenosis rate of 18.1% in the subgroup of patients with geographical mismatch is similar to the corresponding rates for DES inthe treatment of small coronary vessel diseases.

PEPCAD II

The aim of PEPCAD II was to assess the safety and efficacy of SeQuent Please in the treatment of ISR in native coronary arteries in comparison to the paclitaxel-elutingTaxus Liberté stent. The study included 131 patients; 66 were randomized into the DEB group and 65 into the DES group.

The inclusion criteria were patients with ISR in the coronary arteries and stable or unstable angina. Patients with reference vessel diameters between > 2.5mm and <3.5mm and < 22mm in length were included. The primary end-point was LLL at six months, while secondary endpoints included binary restenosis at six months and MACEat six months, 12 months and 48 months. The patients were also put on antiplatelet therapy using clopidogrel (75g daily) for three months in case of DEB and six months incase of DES.

The preliminary study results found in-segment LLL and binary restenosis rates in the current study (0.18 ± 0.41mm/6.7%) which is comparable to the PACCOCATH ISRI/II study (0.14 ± 0.46mm/6.0%) at six months. For the paclitaxel-eluting stent group, the six month binary restenosis rate in the current study is identical to the ISAR-DESIRE study (20.4%). At six months, total MACE rate was 4.7% in the DEB group versus 18.3% in the DES group in the as treated analysis. 12 month target lesionrevascularization in the coated balloon groups of the current study and the PACCOCATH ISR I/II study were similarly very low (5.7%) compared to 16.7% in the stentgroup of this study.

Ongoing Clinical Trials

Table 45: List of Ongoing Clinical Trials, Sequent Please, 2011

Acronym Aim Indications Location Study DesignPlannedPatients



Enrollment

INDICOR

The INDICOR study isa controlled,prospective,multicenter,randomized, two armPhase II real worldstudy assessing theacute, six month, 12month and three yearoutcome of cobalt-chromium stent(Coroflex Blue)deployment followedby paclitaxel-elutingPTCA-balloondilatation (SeQuentPlease) and ofpaclitaxel-elutingPTCA-balloondilatation (SeQuentPlease) followed bycobalt-chromium stent(Coroflex Blue)deployment for thetreatment of de-novoand restenotic lesionsin native coronaryarteries.

Coronaryheartdisease

India

Treatment,randomized,single blind(subject),active control,parallelassignment,efficacy study.

125

PEPCAD-CTO

The aim of the studyis to assess the safetyand efficacy of apaclitaxel-elutingPTCA-balloon incombination with BMSfor treatment ofchronic totalocclusions in nativecoronary arteries withreference diametersof 2.5-4.0mm.

Nativecoronaryartery,chronictotalocclusion,coronaryarterydisease

Germany

Treatment,open label,historicalcontrol, singlegroupassignment,efficacy study.

48

SEDUCE

The trial aims tocompare healingprocesses aftertreatment of BMS ISRwith balloon dilatationusing DEB versusimplantation of DES.

Restenosis Belgium

Treatment,randomized,open label,active control,parallelassignment,safety/efficacystudy.

50

ISAR-DESIRE-3

The aim of the studyis to assess theefficacy of thepaclitaxel-elutingPTCA - ballooncatheter SeQuentPlease to treat ISR ofvarious DES in nativecoronary arteries withreference diametersbetween 2.5mm and= 3.5mm and lesionlengths < or = 22mm.

Restenosis,ischemia,heartdiseases

Germany

Randomized,single blind(outcomesassessor),active control,parallelassignment,safety/efficacystudy,treatment.

375

PEPCAD-DEBonly

The purpose of thisrandomized study isto determine whichtreatment option isthe most effective inthe treatment ofrestenosis afterimplantation of LimusEluting Stents, (LES).

Coronarystenosis

Germany

Randomized,open label,parallelassignment,safety/efficacystudy,treatment.

90

Nospecificacronym

The main objective ofthe study is todetermine whetherPCI for ISR with aDEB isangiographically non-inferior to PCI with aDES at six monthfollow up.

ISRTheNetherlands

Randomized,uncontrolled,parallelassignment,single blind(subject),treatment.

270

The objective of thetrial is to assess the



PEPCAD-BIF

safety and efficacy ofDEB application(SeQuent Please) tothe side branch inpercutaneouscoronary intervention(PCI) of Medina type0,0,1 coronarybifurcation lesions.

CAD Germany

Randomized,active control,efficacy study,parallelassignment,open label,treatment.

120

WinDEB

The objective of thestudy is to show thesafety and efficacy ofthe SeQuent Please(DEB) compared tocommonly used DESin the treatment ofsmall vessel diseaseand side branches bypressure wire guidedPCI.

CAD AustriaParallelassignment,single blind

100

RIBS IV

The objective of thestudy is to assesswhich interventionalstrategy (paclitaxel-eluting balloon versuseverolimus-elutingstent) is superior inthe treatment ofpatients sufferingfrom DES restenosis.

ISRSpain,Austria,Europe

Prospective,randomized,multi center,parallelassignment,single blind(outcomesassessor),efficacy study,treatment.

310

Source: GlobalData, Company Websites, SEC Filings, Investor Presentations, Newsand Press Releases, Scientific Journals, ClinicalTrials.gov

DIOR Paclitaxel-Eluting Coronary Balloon Catheter


DIOR is a drug eluting balloon developed by Eurocor, a subsidiary of Opto Circuits Ltd., and is designed for the treatment of coronary ISR, bifurcated coronary arterylesions, small diameter coronary arteries and coronary stenting in de novo lesions. Eurocor obtained the CE mark for DIOR in 2007 and began marketing the product inEurope. It was launched in Canada in February 2010.

The product is currently undergoing clinical trials for ISR, SVD and bifurcation lesions. It claims to offer patients reduced antiplatelet therapy of three months and toeliminate the need for any stent-in-stent re-intervention. The consequences of mismatch between the double stented and unstented portions of the vessel are avoided.Moreover, the patient remains accessible to re-intervention if needed, without restricting the chance of a successful repeated treatment.

DIOR drug-eluting balloon is loaded with 3.0!g paclitaxel/mm2 into the microporous balloon surface. DIOR is inflated at the lesion site for up to 60 seconds for full drugrelease but may be inflated several times. A first inflation of 20 seconds leads to 35% of paclitaxel release and the second inflation of 20 seconds releases another 35%.

Key Technology

Second generation DIOR uses shellac based bio-coating for binding paclitaxel onto its surface. First generation DIOR used microcrystals following di-methyl sulfatetreatment for the dissolution of paclitaxel. The three-folded DIOR balloon protects the loaded drug from early wash-off during the insertion of the catheter and tracking tothe coronary lesion. The microporous structure of the balloon surface is designed to hold the drug. Paclitaxel prevents restenosis via the depolymerization and stabilizationof microtubular dependent activities such as the suppression of cell division and migration and is known to inhibit inflammatory processes.


DIOR is currently undergoing four clinical trials; Spanish Registry, Valentine’s Trial, DEBUIT and the assessment of DEB for application in acute myocardial infarction. Onlythe results from the Spanish Registry have been published so far.

VALENTINE’S Trial

This was a multi-center, open-label, one-week registry designed to evaluate DIOR in patients with ISR. The DIOR drug-eluting balloon for use in the trial and had managedboth the trial and its investigators via its own organization and the international distributor network. Eurocor’s worldwide real life registry Valentines Trial I was conductedwith an objective to assess the efficacy of the drug eluting balloon.

Paclitaxel-eluting balloon DIOR for ISR derived from a previous stent (BMS/DES) implantation at six to nine months. All data for analysis was collected via an electronicdata capture system and analyzed within the Cardiovascular Research Institute Data Coordinating Center of the Washington Hospital Center.

A total of 300 patients were planned to be enrolled. Primary end point was IRS of a previously placed stent. 32% of participants were diabetes patients and more than 50%presented with long and diffuse ISR.

The results were presented in Cardiovascular Research Technologies (CRT) 2011 Meeting in Washington DC and showed safe and effective treatment of cases of ISR. Theoverall TLR of the target lesion with DIOR DEB after eight months was very low at 7.4% compared to 5.9% for the BMS subgroup and 9.8% for DES. The study resultsfurther showed DIOR DEB to be effective in patients that suffer from diabetes with an average TLR rate of 11.5%.



Piccoleto

The Piccoleto trial was a noninferiority study that randomized patients with stable or unstable angina and small coronary vessels (= 2.75 mm) to PCI with the Dior(Eurocor, Bonn, Germany) paclitaxel-eluting balloon or Taxus Liberté paclitaxel-eluting stents. Patients with stable angina with indication to PCI of a small coronary vessels(<2.75mm) were included in the trial. The aim of the trial was to determine that the paclitaxel eluting balloon would be equivalent to a DES in terms of restenosis for thetreatment of small coronary artery disease. The primary end point was defined at six months Quantitative Coronary Angiography (QCA) (non-inferiority between balloonand stent).

Six month interim results of the Piccoleto trial showed on QCA analysis that patients given the DIOR Paccocath DEB had a percentage diameter stenosis (the primaryendpoint) almost twice that of patients receiving Taxus (43.6 ± 27.4% vs. 24.3 ± 25.1%; P = 0.029). Other angiographic endpoints, such as minimal lumen diameter andbinary restenosis, were also worse with the balloon. In clinical follow up at nine months, there were no cardiac deaths or Academic Research Consortium-defined definiteor probable stent thrombosis in either group. Other clinical outcomes were also equivalent, except for a trend toward increased TLR in the balloon group. Thus, paclitaxel-eluting balloon failed to show equivalence to Taxus stent in terms of angiographic percent restenosis for PCI of small CAD.

DIOR Spanish Registry

The prospective, multicenter registry, spread over nine Spanish centers, aims to assess the efficacy and safety of a new paclitaxel-eluting balloon for the treatment of ISRand SVD. 115 lesions in 110 patients were included with the following indications: ISR (52%); de novo lesions in small vessels (2.5mm) in 43% (including bifurcationlesions) and in patients with a contraindication to DAT (5%). Clinical follow-up was planned at one, six and 12 months, with repeat angiography at six to eight months.

Interim results reveal that at a mean of 3.5 ± 2.2 months, there was only 3.4% MACE. There were no sub-acute thromboses or occlusions. At six months, TLR was found in4.8%, MACE in 7.7% and no patients had thrombosis. In the ISR subgroup, TLR was found in 7.4%, MACE in 11.1% and thrombosis in 0% after six months. For the smallvessel subgroup at six months, TLR revascularization was found in just 2.1% while MACE was observed in 4.3%. No patient was observed to have thrombosis.


Table 46: List of Ongoing Clinical Trials, DIOR, 2011

Acronym Aim Indications LocationStudyDesign

PlannedPatientsEnrollment

DEBUIT

The purpose of theDEBIUT study is toassess procedural,clinical andangiographicoutcomes ofprovisional T-stenting use fordilation thepaclitaxel-elutingPCI-balloon (DIOR)in comparison todilation with astandard balloonprior to the implantof the Liberté BMSin bifurcationlesions (with sidebranchinvolvement). Alsoto compare theresults above withthe results of usinga standard balloonprior to provisionalT-stenting with thepaclitaxel-elutingstent TaxusLiberté.

Stable angina,unstableangina,atherosclerosis,CAD.

TheNetherlands,Belgium

Treatment,randomized,open label,parallelassignment,efficacystudy

120


Elutax


Elutax is a paclitaxel-eluting balloon developed by Aachen Resonance and is intended for the treatment of small lesions and ISR. In 2009, the company signed adistribution agreement with Biotronik for exclusive distribution in Switzerland, Belgium, the Netherlands, Luxembourg, England, Ireland and Italy.

It has been specially designed for coronary arteries and small coronary and peripheral vessels. 20% of the drug is released after each balloon inflation on the surface ofthe balloon. The balloon catheter is made of polyamide and has following features:

Flexible tip design.

Low profile.



Excellent flexibility and optimal pushability.

Soft transition from tip to balloon.

The balloon catheter design is a rapid exchange and triple fold balloon. The catheter comes in a variety of sizes, ranging from 10mm to 39mm for balloon length. Thecatheter is coated with 2!g/mm2 of paclitaxel.

Key Technology

The Elutax balloon is coated with a drug with special technology which does not require the use of a polymer or hydrophilic spacer. Due to the use of only pure paclitaxel tocoat the balloon, complications such as thrombosis are thought to be minimal. The drug is coated in two layers: special ICE-like paclitaxel which serves as an elastic andstable ground layer, and, on top of this, a special SNOW-like paclitaxel layer serves as the drug depot and enables homogenous and reliable drug release. The ICE layer isalso called the elastic mechanical resistance base coating. The catheter also has drug wash off protection through as it is encased in the balloon’s surface and hiddenbetween the folds.

The DEB uses paclitaxel as the anti-restenosis drug which is lipophilic and releases after contact with the vessel wall. In Smooth Muscle Cells (SMC) and Endothelial Cells(EC), effective paclitaxel concentrations inhibit various cell functions, which normally lead to re-stenosis. The drug restrains the function of microtubili and inhibits PlateletDerived Growth Factor (PDGF) and therefore prevents cell proliferation and migration.


Preliminary results from two trials have been released by the company for ISR and peripheral disease.

IASIS CE-Trial (Bulgaria)

43 patients with ISR were treated with Elutax. Angiographic follow-up after six months showed restenosis in 0% of patients.

IASIS PE-Trial (Bulgaria-Italy)

39 patients with various peripheral artery occlusions were treated with Elutax. After six months, angiographic results showed occlusion in 2% of the patients, while 7%suffered from non-significant stenosis.

No information is currently available for other ongoing Elutax trials.

Moxy Drug Coated Balloon Catheter


Moxy Drug Coated Balloon Catheter is a DEB catheter intended to be used in the treatment of coronary stenosis caused by atherosclerosis, developed by Lutonix. It isdesigned to deliver paclitaxel to the arterial wall in a single, short inflation arterial restenosis. It combines angioplasty and stenting procedures with on-site debris removal.It is a type of soft catheter with an inflatable balloon at its tip which is used during a catheterization procedure. It is designed to enlarge a narrow opening or passagewithin the artery. The deflated balloon catheter is positioned, the balloon is expanded and deflated, pushing the plaque against the artery wall and widening the artery.When the artery has opened enough to allow sufficient blood flow, the catheter and balloon are removed.

Key Technology

The Moxy drug-coated balloon catheter is a standard angioplasty balloon with a special coating consisting of paclitaxel and a proprietary drug carrier. Paclitaxel is a drugwhich prevents restenosis due to cellular proliferation that can cause arteries to re-narrow after the procedure. Moxy balloon uses a proprietary carrier which helpstransfer the drug to the tissue of the arterial wall upon balloon inflation. Moxy’s drug carrier is a molecular entity on the FDA IV-approved list. The drug carrier hasfollowing features:

High drug retention on the balloon during transit to the target lesion.

Optimal drug release from the balloon catheter during inflation at the targeted treatment site.

High drug transfer efficiency to the vessel wall.

Minimized systemic drug exposure.


PERVIDEO I

The objective of the study is to investigate the feasibility, safety, and efficacy of the Lutonix catheter in the native coronary system. The two year study enrolled 41subjects between June and December 2009 at clinical sites in Belgium, Germany and the Netherlands. The target population for this study was patients who presentedanginal symptoms due to a restenosis within a previously placed BMS in a coronary artery, for which the Moxy balloon is being tested as alternative treatment. Primaryend points for the study included LLL of the target lesion by Quantitative Vascular Angiography (QVA), clinically driven TLR of the target lesion in the amputation freesurviving patients and composite of all cause death, major amputation and clinically driven TLR.

Six month results for this clinical trial were released at the 2010 Transcatheter Therapeutics Conference in September in Washington D.C. The post procedure diameterstenosis in patients was found to be 27.5% and after six months the diameter stenosis was 35.6%. Percentage change in diameter stenosis was found to be low at 8.5% atsix months. The in-segment LLL was found to be 0.16 +/- 0.44mm.

Optical Coherence Tomography (OCT) Study



The objective of the trial is to assess the feasibility, safety and efficacy of the Lutonix catheter for treatment of de novo coronary artery stenosis using two distincttreatment strategies. The two year study enrolled 26 subjects between July and November of 2009 at three clinical sites in the Netherlands. The target population for thisstudy was patients who presented symptomatic de novo coronary lesion. The objectives of this study were to utilize a highly specific imaging technology, OpticalCoherence Tomography (OCT), to measure the biological effect of the Moxy balloon, and to establish the safety of the Moxy balloon when used in conjunction with a BMS.One set of patients were subject to DEB before BMS implantation while other set of patients were subject to DEB after BMS implantation. The results were compared in bothsets.

Six month results for this clinical trial were released at the 2010 Transcatheter Therapeutics Conference in September in Washington D.C. LLL was found to be 0.53mm withDEB administered before BMS implantation while patients with DEB after BMS were found to have only 0.45mm of LLL.

LEVANT I

The objective of the study is to assess the safety and efficacy of the Lutonix catheter for treatment of stenosis of the femoropopliteal arteries by direct comparison tostandard balloon angioplasty. 101 patients were recruited with a single de novo or restenotic atherosclerotic lesion greater than or equal to 70% in the SFA or poplitealartery that is greater than or equal to 4cm and less than or equal to 15cm in total length. Reference vessel diameter considered was greater than or equal to 4 mm andless than or equal to 6mm.

The interim results of the trial showed the Moxy balloon had the ability to safely and substantially inhibit restenosis. Six month average late lumen loss, the trial's primaryend point, was 0.46mm in patients in the paclitaxel-coated-balloon group, compared to 1.09mm for the conventional-angioplasty control group (p=0.016). There was also anon-significant trend in favor of the drug-coated balloon for TLR, 13% versus 22%. At six months, 72% of the drug-coated-balloon group had patent vessels, defined as<50% diameter stenosis with no TLR, compared to 49% of the control group. There were no thromboses in the drug-coated-balloon group and two in the regular-balloongroup. LLL and patency rates were better with the drug-coated balloon in both the stented and non-stented patients; however the study was not designed to showdifferences in those subgroups.


Table 47: List of Ongoing Clinical Trials, Moxy Drug Coated Balloon

Catheter, 2011

Acronym Aim Indications Location Study DesignPlannedPatientsEnrollment

LEVANTII

The trial aims to comparethe safety and efficacy ofthe Moxy balloon tostandard balloonangioplasty for thetreatment offemoropopliteal disease ina large patient population.

PVD The US

Randomized,multicenter,treatment,safety andefficacy study

476


Global PTA Drug Eluting Balloons Market - Key Marketed Products

Cotavance

Product Description

Cotavance is a DEB angioplasty catheter intended to be used in patients with PVD. It is based on PACCOCATH technology which applies a drug matrix to balloon of anangioplasty catheter. When the catheter is inflated to dilate the narrowed vessel, an anti-restenotic drug is released directly to the diseased area. This device keeps thevessels open wider for longer. The company recently announced a co-marketing agreement with B. Braun for PACCOCATH technology. The product was launched in May2011 in Europe and the Middle East following CE approval.

Key Technology

Cotavance uses the proprietary matrix technology PACCOCATH, which provides a unique matrix of paclitaxel and a hydrophilic spacer on the surface of the balloon. Thematrix comprises the anti-restenosis drug paclitaxel and the radiological contrast agent Ultravist 370. The creates a large contact surface area between the lipophilic drugand the vessel wall, as well as a high bioavailability of paclitaxel at the target site for rapid drug absorption by the vessel wall. This allows the uniform and completeapplication of the drug after the first balloon inflation. After inflation, the matrix dissolves immediately so that no material is left behind that could potentially lead tocomplications..

Bayer Schering Pharma AG is the owner of the PACCOCATH trademark and technology and is developing it for market through the Bayer affiliate, MEDRAD Inc. under thebrand name Cotavance,


These studies were originally performed in Sequent Please by B. Braun. However, Medrad and B. Braun has now signed a co-marketing agreement wherein B. Braun willuse the technology to manufacture PTCA DEB while MEDRAD with explore opportunities in PTA DEB market with Cotavance. It also announced the recruitment of physiciansfor US clinical trials for PACCOCATH technology.

THUNDER TRIAL

The THUNDER trial was one of the first trials to test the efficacy of local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. 154 patients were enrolled



for the study with 54 assigned to the control group, 48 to treatment with paclitaxel-coated balloons and 52 to treatment with paclitaxel in the contrast medium.

Inclusion criteria included all patients with one or more obstructive lesions, either new lesions or restenosis, of at least 70% of the vessel diameter and at least 2cm inlength, in the superficial femoral artery, the popliteal artery or both. Patients with poor inflow, the absence of a patent crural artery, an acute onset of symptoms,pregnancy, life expectancy of less than one year and contraindications to the required medication were excluded. The primary endpoint was LLL at six months. Thesecondary endpoints were angiographic restenosis, changes in the Rutherford classification, the ankle-brachial index, patency rate, and the incidence of TLR. The primaryend point of mean LLL was significantly lower in the group treated with paclitaxel-coated balloons than in the control group (0.4±1.2mm versus 1.7±1.8mm). In contrast,LLL in the group receiving paclitaxel in the contrast medium (2.2±1.6mm) did not differ significantly from the control group. LLL reached 1.9±1.8mm in the control group(39 patients), 0.3±1.1mm in the group treated with paclitaxel-coated balloons (39 patients versus the control group), and 2.1±1.6mm in the group treated with paclitaxel inthe contrast medium.

In conclusion, use of paclitaxel-coated balloon catheters significantly lowered the incidence of restenosis at six months and the rate of target-lesion revascularization at six,12 and 24 months. In contrast, the addition of paclitaxel to the angiographic contrast medium did not have a significant effect.

PACCOCATH FEM

The aim of the pilot study was to evaluate a local drug delivery in femoropopliteal artery offered by DEB versus a conventional uncoated balloon. This blinded, randomized,multicenter study enrolled 87 patients in Rutherford class one to four with occlusion or hemodynamically relevant stenosis, restenosis, or ISR of the femoropoplitealarteries.

Eligible patients had an occlusion or stenosis 70% diameter of the superficial femoral artery and/or the popliteal artery with clinical Rutherford stage one to five. Theprimary end point was LLL at six months by quantitative angiography. Secondary end points included the restenosis rate in the treated lesion at the six month follow-upangiography, target lesion revascularization, the change in mean ankle brachial index, the difference between the Rutherford class at baseline and at the six month visitand amputation.

At six months follow-up, the LLL was 0.5±1.1mm in the paclitaxel-coated balloon group and 1.0±1.1mm in the control group. Restenosis developed in 16 out of 34 patients(47%) in the control group and six out of 31 patients (19%) in the paclitaxel-coated group.


Table 48: List of Ongoing Clinical Trials, Cotavance, 2011


EUROCANAL

The trial aims toidentify andcharacterizetherapeutic andfunctional endpointassessments insubjects withdocumented CLI whoreceived treatmentwith the Cotavancepaclitaxel coatedballoon versus thosewho received PlainOld BalloonAngioplasty (POBA)only.

CLI EuropeSafety/efficacystudy,treatment.

120

DEFINITIVEAR

The objective of thisstudy is to evaluatethe use of either theTurboHawk orSilverHawk systemsfollowed by treatmentwith the CotavanceDEB catheter versusthe Cotavanceballoon catheteralone in patients withPVD.

PVD US

Randomized,parallelassignment,double blind,treatmentstudy.

125

COPACABANA

The aim of the studyis to investigateCotavance Paccocathversus uncoatedballoon angioplastyfor the treatment ofISR in peripheralarteries.

ISR inperipheralarteries.

US

Investigatorsponsoredprospective,multi-center,randomizedtrial.

NA

RIVER

The goal of the studyis to evaluate thesafety and efficacy ofpaclitaxel-coatedballoon angioplastyusing the proprietaryPaccocath technology(Cotavance, MedradInterventional/Possis)versus POBA for the

Restenosis inatheroscleroticlesions of thefemoropopliteal

US

Prospective,multicentre,randomizedtrial.

NA



prevention ofrestenosis inatheroscleroticlesions of thefemoropoplitealarteries.

arteries.

CANAL

The objective of thestudy is to comparePOBA with Cotavancefor infrapopliteallesions in CLI.

Infrapopliteallesions in CLI.

USProspectivestudy.

NA

Source: GlobalData, Company Websites, SEC Filings, Investor Presentations, News andPress Releases, Scientific Journals, ClinicalTrials.gov

IN.PACT Paclitaxel Eluting Balloon Catheter Series

Product Description

IN.PACT paclitaxel eluting balloon catheter series, developed by Invatec, Inc. is intended to treat atherosclerosis in the arteries located below the knee. The companyreceived the CE mark for the treatment of ISR. The IN.PACT series includes Amphirion, Admiral and Pacific DEBs. IN.PACT Admiral and Pacific DEBs are indicated fortreatment for superficial femoral artery while Amphirion balloon is indicated for infrapopliteal interventions.

IN.PACT features FreePac, which is a coating that frees and separates paclitaxel molecules and facilitates their absorption into the wall of the artery. IN.PACT Amphirionenables the treatment of diffuse lesions to the very distal foot arteries (pedal and plantar arteries). The product has the following features:

Over The Wire (OTW) design with full-length shaft push ability.

Unique balloon sizes: 2.0mm-4.0mm diameters available in 40mm, 80mm and 120mm lengths, which allow for one step dilation for long lesions.

Proprietary shaft designed for optimized trackability and pushability, specifically for the treatment of infrapopliteal lesions.

Balloon conformability of FLEXITEC Ultra balloon material which provides the maximum flexibility.

Key Technology

All IN.PACT DEBs are paclitaxel-eluting balloon catheters featuring FreePac drug coating technology. It is a hydrophilic coating that frees and separates paclitaxelmolecules. It also balances hydrophilic and lipophilic properties and facilitates the absorption of paclitaxel into the wall of the blood vessel, and reduces the total drugelution time to 30-60 seconds.

The DEB has been built on the Amphirion DEEP balloon platform, and has an OTW catheter design. Amphirion DEEP balloon platform is specially tuned for ExtremitiesExtreme Angioplasty (EEA). It combines special shaft and balloon technologies to best reach, adapt and treat challenging vascular districts from the infrapopliteal down tothe foot arteries (pedal and plantar arteries). Amphirion DEEP provides conformability of 120mm long balloons combined with 0.017" entry profile and enables thetreatment of diffuse lesions to the very distal foot arteries.


The product is currently undergoing a clinical trial for the treatment of below the knee CLI. The preliminary results were presented at the Leipzig Interventional Coursemeeting in Leipzig, Germany in January 2010.

INPACT DEEP

This is a prospective, multi-center, randomized trial of symptomatic patients with CLI secondary to atherosclerotic lesions (stenotic or occluded) of the infrapoplitealvessels. Patients will undergo a percutaneous transluminal endovascular procedure with either the IN.PACT Amphirion DEB or with a standard PTA balloon. The targetenrollment for the study is 357 patients.

The major inclusion criteria for the study is chronic CLI with Rutherford Category 4, 5 or 6, reference vessel diameter 2-4mm and single or multiple lesions with !70%diameter stenosis. The primary endpoints are LLL at 12 months, clinically driven TLR at 12 months, and major adverse events defined as a composite of all cause death,major amputation and clinically driven TLR. Major secondary end points include amputation-free survival and wound healing, walking capacity assessment versus thebaseline and MACE.

On January 29 2010, Invatec announced the first clinical results for the use of the IN.PACT Amphirion paclitaxel-eluting balloon for complex CLI in below-the-knee vessels.The preliminary results indicate a dramatic reduction in the restenosis rate with the application of the device. IN.PACT Amphirion reduced restenosis in CLI patients withlong lesions to 31% at three months compared to 69% with standard PTA balloon. The outcome seems to be positive in light of the mean lesion lengths of 17cm and a 58%rate of total occlusions before intervention in the study.


Table 49: List of Ongoing Clinical Trials, IN.PACT Series


IN.PACTSFA I

The objective of thisstudy is to evaluate thesafety and efficacy ofthe IN.PACT Admiral

Proximalpoplitealarterial Global

Randomized,parallelassignment, 150



drug eluting PTAballoon.

disease andSFA

open labeltreatment.


FREEWAY 014

Product Description

FREEWAY 014 paclitaxel eluting peripheral dilatation catheter is a drug-eluting catheter intended to be used in the prevention of restenosis in patients with PVD. It is coatedwith a paclitaxel, which is known to interfere with the process of restenosis. It is absorbed by the arterial wall at the lesion site while the FREEWAY balloon is inflated for upto one minute at nominal balloon dilation pressure. Multiple balloon inflation may be applied for total drug release.

Key Technology

The FREEWAY 014 Bioshell coating matrix consists of a natural resin, which is EMEA and FDA approved Generally Recognized As Safe (GRAS) as food additive under E 904.The film forming properties of shellac are used to coat gastric resistant tablets. Shellac is a natural resin composed of shellolic and aleuritic acid. The coating consists of a1:1 mixture of paclitaxel with shellac applied to the balloon by a micro-pipetting procedure in a clean room under sterile conditions. Tissue concentrations of paclitaxelreached by this coating is inflation time dependent, after 60 seconds or more of inflation a concentration of 200µM/L can be reached.


No clinical results were found.

Ongoing Clinical Study Results

Table 50: List of Ongoing Clinical Trials, FREEWAY


FREERIDE NAStenotic andrestenotic lesions inSFA.

GlobalInternationalprospectiverandomized study.

280


Global Drug Eluting Balloons Market - Strategic Pipeline Assessment

Pipeline Technology Assessment

Pipeline Technology Assessment for Drug Eluting Balloons by Development Stage for PTCA

Figure 46: Pipeline Technology Assessment for PTCA Coronary Drug Eluting Balloons

by Development Stage, Europe, 2011



Source: GlobalData, Company Websites, SEC Filings, Investor Presentations, News and PressReleases, Scientific Journals, ClinicalTrials.gov, Interviews with Industry Experts and Key OpinionLeaders (KOLs)

Nearly 75% of all pipeline products for PTCA DEBs in Europe are first-in-class. Seven of eight of these products are in the clinical Phase and one is one product in the earlydevelopment Phase. The single product in the me-too category is a paclitaxel based DEB. There are at present seven product extensions in the pipeline. The productextension pipeline product such as second generation DIOR paclitaxel eluting balloons are working on improving drug delivery. Already approved products are also beingstudied for more clinical applications. Clinical trials using the IN.PACT Falcon in the treatment of de novo coronary lesions and SVD are also being planned by Invatec.DIOR, currently approved for ISR, is being studied for applications in bifurcation lesions and acute myocardial infarction. SeQuent Please is available in the EU and iscurrently undergoing clinical trials for indications such as bifurcation lesions, small vessel coronary disease and PVDs. The product is also being studied for efficacy ofintervention using DEBs along with BMS.

There are no DEBs in the market in the US, hence all are considered first in class. Clinical trials are currently being conducted to determine efficacy.

Figure 47: Pipeline Technology Assessment for PTA Drug Eluting Balloons by

Development Stage, Europe, 2011

Source: GlobalData, Company Websites, SEC Filings, Investor Presentations, News and PressReleases, Scientific Journals, ClinicalTrials.gov, Interviews with Industry Experts and KeyOpinion Leaders (KOLs)

A total of seven PTA DEB products are currently in the pipeline. Six are in the clinical development stage while one is in the early development. All PTA DEB balloons arepaclitaxel eluting balloons. PTA DEB products have been only recently launched in Europe following PTCA balloons. Over the last two years, Boston Scientific has alsoentered the market with its product Boston DEB.

As no product has been FDA approved, all PTA DEBs are considered first-in-class in the US.

Pipeline Technology Assessment for Drug Eluting Balloons by Unmet Need

Figure 48: Pipeline Technology Assessment for Drug Eluting Balloons by Unmet

Need



Source: GlobalData, Company Websites, SEC Filings, Investor Presentations, News and PressReleases, Scientific Journals, ClinicalTrials.gov, Interviews with Industry Experts and Key OpinionLeaders (KOLs)

The first-in-class DEBs represented above have novel mechanisms of action and are expected to have better efficacy and safety profiles. A number of early developmentand preclinical stage pipeline products are experimenting with rapamycin (Sirolimus) and genistein as alternatives to paclitaxel. Another unique mechanism of actionpertaining to first-in-class DEBs is the difference in drug coating technology used. Better technologies are expected to increase the efficacy of the product as it reduces theamount of the drug lost in transition. Moreover, the controlled drug release enabled in newer drug coating technologies prevents the incidence of embolism due to thebursting of drug particles from the balloon catheter and toxicity due to drug overdose.

The me-too DEBs have similar characteristics to the marketed products in that they use paclitaxel as the anti-restenosis drug of choice. Products such as Cotavance usealready established drug coating technology such as PACCOCATH, which is used presently in SeQuent Please DEB by B. Braun.

Product extension pipeline products are currently trying to enhance their usage by expanding the indications in which they can be used successfully as intervention.

Novel Pipeline Technology Assessment for Drug Eluting Balloons

Novel Anti-Restenosis Drugs

A number of companies are exploring the use of alternative anti-restenosis drugs, such as a sirolimus, genistein, rapalog and NF-kappa B decoy. Caliber Therapeutics, Inc.is exploring rapalog-based DEB technology, which the company claims will provide benefits through sustained drug release over time. To combat the narrowsafety/efficacy window of paclitaxel, currently marketed products use high doses of the drug that can be potentially cytotoxic. Some companies such as AnGes MG havecome up with novel anti-inflammation drugs which have shown efficacy in porcine arteries.

Drug Coating/Binding Technologies

Another area of discovery currently being explored is the drug coating formulations. These formulations can potentially enable controlled release of the drug, which can beused to customize the dosage for the patient. Moreover, the formulation can prevent the premature release of the drug to maintain drug dosage efficacy in vivo andfacilitate the rapid uptake of the drug into the vessel wall upon inflation. The currently marketed products also differ in the way they bind paclitaxel to the balloon. Whilesome products like Elutax does not use any formulation, SeQuent Please, Cotavance and IN.PACT use hydrophilic spacers such as urea. Lutonix is currently testing itsnovel drug coating technology for high safety and efficacy. Biotronik, a recent entrant in the DEB market with Passeo-18 Lux uses Butyryl Tri-Hexyl Citrate (BTHC) as acarrier for paclitaxel. Eurocor recently entered into a distribution agreement with Micell technologies to develop sirolimus-based DEBs with Micell’s proprietary drug deliveryplatform.

Profiles of Promising Products under Clinical Development

Advance 18PTX

Product Description

Advance 18 PTX (paclitaxel) balloon catheter is a DEB intended to treat PVD. It is paclitaxel-coated catheter that treats lesions in the superficial femoral artery andpopliteal artery.

Product Status

The product is currently in the clinical stage.

Clinical Trial Details



Table 51: Advance 18 PTX Balloon Catheter - Advance 18PTX Balloon

Catheter Study: Treatment of Lesions in Superficial Femoral

Artery/Popliteal Artery with a Paclitaxel-Coated Balloon

Trial NameAdvance 18PTX Balloon Catheter Study: Treatment of Lesions inSuperficial Femoral Artery/Popliteal Artery with a Paclitaxel-coatedBalloon

Indications Peripheral arterial disease

Applications Percutaneous transluminal angioplasty

Trial Phase -

Trial Status: Recruiting

TrialObjective

The Advance 18 PTX Balloon Catheter study is a clinical trial to studythe safety and effectiveness of the Advance 18 PTX Balloon Catheter inthe treatment of lesions in the superficial femoral artery and poplitealartery.

Trial Design Treatment, randomized, open label, parallel assignment

TargetPatients

100

ActualPatientRecruited

To be announced

UniquePhysicianIdentifier

NCT00776906

PrimaryPoint

Evaluation of LLL [ Time Frame: six months] [Designated as safetyissue: No ]

SecondaryPoint

There are no secondary measures for this study.

Acronym No specific acronym

ParticipantsInclusion

Age >18 years.

Able to provide informed consent.

Has at least one de novo or restenotic lesion(s) with > 70% stenosisdocumented angiographically of the SFA or popliteal artery. If morethan one lesion requires intervention, only one should be treated as astudy lesion.

ParticipantsExclusion

Has significant stenosis (> 50%) or occlusion of inflow tract (proximalipsilateral, iliofemoral, or aortic lesions) not successfully treated beforethis procedure.

Lack of at least one patent runoff vessel with < 50% stenosisthroughout its course.

Lesions in target area requiring atherectomy (or ablative devices),cutting balloons, cryoplasty balloons, or any other advanced device tofacilitate angioplasty balloon or stent delivery.

Interventions Device: Advance 18PTX Balloon Catheter

Device: Advance 18LP Balloon Catheter

Trial Results To be announced

Source: GlobalData

Genesis DESA Catheter

Product Description

Genesis DESA is a standalone device in the treatment of CAD and PVD stenosis and restenosis via scoring and local drug delivery without the use of a stent. It has a stent-like structure with a nitinol mesh braid over the balloon which creates microfractures in the plaque and allows drugs to be delivered. It will score the plaque and deliver thedrug. It combines both drug elution and scoring.

Dramatically lessens vessel injury.

Diminishes the incidence of dissections.

Causes less barotrauma.

Creates homogeneous compression of the plaque.

Creates more lumen gain versus POBA.



Reduces the incidence of geographic miss or balloon slippage.

Product Status

The product is currently in the pre-clinical stage.


The product is not currently involved in any active clinical trials.

Drug-Eluting PTA Balloon Catheter

Product Description

The drug-eluting PTA balloon catheter being developed by AnGes MG is a catheter with an inflatable balloon at its tip intended for the treatment of PVD. It is designed toprevent the restenosis of a blood vessel after the balloon is inflated, which often occurs in the peripheral blood vessel of patients with dialysis shunt or arteriosclerosis. Thecatheter is coated on the outer surface with anti-inflammatory agent NF-kappa B decoy. NF-kappa B decoy contains biocompatible macromolecular Poly-Lactic-Co-GlycolicAcid (PLGA) nano-particles (200nm).

Product Status

The product is currently in the pre-clinical stage.


The product is currently not involved in any active clinical trials.

Drug-Eluting Balloon

Product Description

The product, developed in collaboration with Caliber Therapeutics and DSM Biomedical, will feature a novel approach for the controlled and sustained release of drugs totreat vascular diseases such as atherosclerosis. The partnership brings together proprietary technology from DSM on drug delivery with balloon and catheter technologyfrom Caliber Therapeutics to develop a DEB. According to the agreement, DSM Biomedical granted Caliber Therapeutics a worldwide exclusive license for the use of DSM'srecently launched Trancerta Drug Delivery platform for the development of this specific application.

The drug delivery balloon catheter is used to treat atherosclerosis. It enables the controlled and sustained release of drugs. It reduces the thrombosis risk and alsoreduces the need to implant permanent devices. The device allows superior drug transfer efficiency into the vessel wall and opens up multiple cardiovascular indicationsthat are inaccessible by stenting.

Product Status

The product is currently in the early development stage.



PTCA Balloon Genistein-Coated Balloon Catheter

Product Description

The genistein-coated balloon catheter developed by Sahajanand Medical technologies Pvt. Ltd. is a DEB intended to reduce restenosis after PCI. It is coated with an anti-restenotic drug called genistein to prevent re-narrowing of the coronary artery following stent placement.

Product Status

The product is currently in the early development stage.



Published results from an animal study on piglets in 2008 demonstrated the in vivo anti-inflammatory effects of a genistein-eluting balloon in PCI.

Global Drug Eluting Balloons Market - Strategic Deals Analysis

Key Acquisitions



Medtronic Acquired Invatec

In 2009, Medtronic Inc, a medical device company, signed a definitive agreement to acquire Invatec SpA, a developer of medical technologies for the interventionaltreatment of cardiovascular disease along with two affiliated companies, Fogazzi and Krauth Cardiovascular GmbH. Fogazzi is a supplier of polymer technology to Invatecand Krauth Cardiovascular distributes Invatec’s products in Germany.

The transaction includes a purchase consideration of approximately $500m consisting of initial payment of $350m and additional payments of up to $150m based onInvatec’s achievement of specific milestones.

Strategic Rationale

The transaction will enable Medtronic to expand its product offering for cardiovascular interventions with the addition of new products for the coronary and peripheralvascular markets. The deal also provides Medtronic with a wide portfolio of Invatec’s DEBs.

MEDRAD Completes Acquisition of Possis Medical

In 2008, MEDRAD, Inc., an affiliate of Bayer HealthCare, through its wholly-owned subsidiary Phoenix Acquisition Corp., completed the acquisition of all outstanding sharesof Possis Medical, Inc., a developer of medical devices for cardiovascular and vascular treatment markets, for a purchase consideration of approximately $361m. With theacquisition, the company also acquired Possis’ balloon catheter portfolio.

Under the transaction, Possis Medical's 15,666,691 shares were validly tendered representing 92% of the outstanding common stock of Possis Medical. The shares havebeen offered at $19.50 per share, representing a premium of approximately 39% over Possis Medical’s average closing price for the thirty days prior to February 8, 2008.

Following the transaction, Possis Medical is now a wholly-owned subsidiary of MEDRAD and Possis Medical’s common stock ceased to be traded on the NASDAQ.

Strategic Rationale

The acquisition will enable both companies to further expand their presence in the cardiovascular intervention field.

Opto Circuits Acquired Eurocor

Opto Circuits India Limited, a company engaged in the manufacturing of healthcare equipment, acquired Eurocor GmbH, a company engaged in the research, developmentand manufacture of interventional cardiology products, for a purchase consideration of !11m in 2005.

Following the acquisition, EuroCOR now operates as a wholly owned subsidiary of Opto Circuits India.

Strategic Rationale

This acquisition will enable Opto Circuits India to expand its market share and improve its shareholder value.

Key Partnerships

Cardiovascular Systems Enters into an Agreement with Invatec

Cardiovascular Systems, Inc. (CSI), a developer of medical devices for treating cardiovascular disease, entered into an agreement with Invatec s.r.l., a developer ofcardiovascular and vascular interventional tools. Under the terms of the agreement, CSI will market Invatec’s PTA balloon catheter line in the US.

Under the agreement, CSI will offer the Invatec balloon catheter line, including the SubMarine Plus PTA Balloon Catheter, the Admiral Xtreme PTA Balloon Catheter and theAmphirion Deep PTA Balloon Catheter.

Strategic Rationale

The agreement will enable Invatec to expand its distribution network in the US. Once approved by the FDA, the company can leverage CSI’s distribution network to marketthe DEBs.

Maxcor Enters into a Strategic Agreement with Micell Technologies

Maxcor Inc., the newly incorporated subsidiary of Opto Circuits (OCI) Ltd, entered into a strategic agreement with Micell Technologies in January 2009. The agreement willprovide the rights to Maxcor’s Genius MAGIC Cobalt Chromium Coronary Stent System to Micell Technologies for the purpose of developing and marketing sirolimus basedDES based on Micell’s proprietary coating technology. The companies also entered into an agreement to develop DEB products for cardiovascular applications. The stentand delivery system was developed and is marketed in Europe by EuroCor GmbH, a subsidiary of Opto Circuits. The specific terms of the agreements have not beendisclosed.

Micell’s technology provides for a unique drug delivery platform within bioabsorbable polymers. The company has developed a drug-polymer formulation that can preciselyand consistently control drug elution and the duration of polymer exposure. As a result, Micell’s coating has the potential to deliver a precise therapeutic solution for CADwithout the long-term safety concerns of the currently available drug-eluting stents and balloons.

Strategic Rationale

The collaboration will provide the companies with the opportunity to develop unique DES and DEBs with controlled drug release.

Eurocor Enters into a Distribution Agreement with Goodman

Goodman Co., Ltd. (Goodman), a company engaged in the development, manufacturing and distribution of vascular interventional devices, has entered into an exclusivefour year distribution agreement with Eurocor GmbH, a researcher, developer and manufacturer of interventional cardiology products, for the distribution of DES and DEB



products in the Japanese domestic market.

Goodman is a medical device company engaged in the development, manufacturing and sale of cardiology products in the areas of medical equipment and medicaldisposables. The company’s product line includes intravascular treatment catheters, intravascular diagnostic catheters, medical diagnostic equipment and artificial organs.Goodman operates its business in Japan, China, Korea, the US and Ireland through two subsidiaries, namely Avantec Vascular Corporation and LightLab Imaging, Inc. It isheadquartered in Nagoya, Japan.

Strategic Rationale

The agreement expands Eurocor’s influence in Japan.

MEDRAD Enters into Licensing Agreement with B. Braun Melsungen

MEDRAD, INC., a manufacturer of medical devices and an affiliate of Bayer Schering Pharma AG, entered into a co-marketing and trademark license agreement with B.Braun Melsungen AG, an operator of dialysis centers, to promote the PACCOCATH technology.

Under this agreement, B. Braun is permitted to use the PACCOCATH trademark in connection to promotion and marketing of its DEB products. Both companies will use thePACCOCATH technology in DEBs and also feature it at various trade shows, sponsored educational seminars and symposia and on informational websites.

The PACCOCATH technology is a proprietary drug matrix applied to the balloon of an angioplasty catheter. The PACCOCATH technology has been shown in multiple clinicaltrials to keep the artery open wider (reducing LLL) over time in patients with PVD and CAD. Bayer Schering is the owner of the PACCOCATH trademark and technology.

Strategic Rationale

This collaboration enables both partners to promote a breakthrough medical treatment for cardiovascular disease by using the Paccocath technology.

DSM Biomedical and Caliber Therapeutics Form Partnership

In September 2008, Royal DSM N.V., the global life sciences and materials sciences company headquartered in the Netherlands, announced that its subsidiary DSMBiomedical and Caliber Therapeutics, Inc. will partner on the development of a novel drug delivery balloon catheter that can be used to treat vascular diseases such asatherosclerosis.

The device is being developed by DSM Biomedical and Caliber Therapeutics and will enable the controlled and sustained release of drugs to treat vascular diseases such asatherosclerosis. The partnership will combine proprietary technology from DSM Biomedical on drug delivery with balloon and catheter technology from CaliberTherapeutics. In addition, DSM Biomedical will grant Caliber Therapeutics a worldwide exclusive license for the use of DSM’s recently launched Trancerta Drug Deliveryplatform for the development of this specific application. The Trancerta drug delivery platform will be developed further to deliver an optimal therapeutic drug dose fromCaliber’s TADD balloon, combining safety and efficacy. Trancerta covers an extensive portfolio of advanced resorbable materials, synthesis methods and formulation andprocessing techniques, which provide the foundation for designing tailored drug delivery systems.

Strategic Rationale

The partnership will enable both companies to leverage their respective expertise to develop highly efficacious drug eluting balloon.

Aachen Resonance Enters into a Distribution Agreement with Biotronik

In January 2009, Aachen announced a distribution agreement with Biotronik for Elutax to Switzerland, Belgium, the Netherlands, Luxembourg, England, Ireland and Italy.

Biotronik has a strong presence in these geographies and currently offers products in cardiac rhythm management and vascular intervention areas. The deal will expandAachen’s presence in Europe, where the product has recently gained CE approval.

Appendix

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Definitions

PTCA Coronary Drug Eluting Balloons (DEB)

DEBs are PTCA or PTA balloons coated with an anti-restenosis drug such as paclitaxel. They are used to open narrowed and diseases arteries. The drug is released uponinflation of the balloon which blocks SMC proliferation in the vessel. They are drug/device combinations.

PTA Peripheral Drug Eluting Balloons (DEB)

Drug Eluting Balloon is a anti-restenosis drug coated PTCA balloon which is intended to prevent re-narrowing of the coronary artery after stent placement. It is designed forthe intraluminal drug application in coronary arteries and peripheral vessels to treat In-Stent Restenosis (ISR), bifurcations, small vessels, and long lesions. One unit refersto one PTA Peripheral Drug Eluting Balloons (DEB).

Acronyms

ACE: Angiotensin-Converting Enzyme

BMS: Bare Metal Stents

BP: Blood Pressure

BTHC: Butyryl Tri-Hexyl Citrate

CAD: Coronary Artery Disease

CAGR: Compound Annual Growth Rate

CBA: Cutting Balloon Angioplasty

CE: Conformité Européenne

CLI: Critical Limb Ischemia

CRT: Cardiovascular Research Technologies

DAT: Dual Antiplatelet Therapy

DEB: Drug Eluting Balloon

DES: Drug Eluting Stents

EC: Endothelial Cells

ECG: Electrocardiogram

EEA: Extremities Extreme Angioplasty

FDA: Food & Drug Administration

HDL: High-Density Lipoprotein

ISR: In-Stent Restenosis



GRAS: Generally Recognized As Safe

LDL: Low-Density Lipoprotein

LES: Limes Eluting Stents

LLL: Late Lumen Loss

LSM: Late Stent Malapposition

M&A: Mergers and Acquisitions

MACE: Major Adverse Cardiac Events

OCT: Optical Coherence Tomography

OTW: Over The Wire

PAD: Peripheral Artery Disease

PCI: Percutaneous Coronary Intervention

PDGF: Platelet Derived Growth Factor

PLGA: Poly-Lactic-Co-Glycolic Acid

POBA: Plain Old Balloon Angioplasty

PTA: Percutaneous Transluminal Angioplasty

PTCA: Percutaneous Transluminal Coronary Angioplasty

PVD: Peripheral Vascular Disease

QCA: Quantitative Coronary Angiography

QVD: Quantitative Vascular Angiography

SMC: Smooth Muscle Cells

SVD: Small Vessel Disease

TLR: Target Lesion Revascularization

TVR: Target Vessel Revascularization

Sources

American Heart Association

American heart.org

Centers of Medicare and Medicaid Services

Federal Interagency Forum on Aging-Related Statistics

International Society for Pharmacoeconomics and Outcomes Research

Inter-Society Consensus for the Management of PAD (TASC)

Journal of Vascular Surgery

National Institutes of Health (US)

National Institutes of Health: National Information Center on Health Services Research and Health Care Technology

The Journal of Invasive Cardiology

US Department of Health and Human Services

US National Library of Medicine

Vascular Disease Foundation

Research Methodology

GlobalData’s dedicated research and analysis teams consist of qualified professionals with experience in marketing, market research, consultancy (with a background inthe medical devices industry) and advanced statistical expertise.

GlobalData adheres to the codes of practice of the Market Research Society (www.mrs.org.uk) and the Society of Competitive Intelligence Professionals (www.scip.org).



All GlobalData databases are continuously updated and revised. The following research methodology is followed for all databases and reports.

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Company websites, annual reports, financial reports, broker reports, investor presentations and SEC filings.

Industry trade journals, scientific journals and other technical literature.

Internal and external proprietary databases.

Relevant patent and regulatory databases.

National government documents, statistical databases and market reports.

Procedure registries.

News articles, press releases and web-casts specific to the companies operating in the market.

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Models

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Available hard data is cross referenced with the following data types to produce estimates:

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Forecasts

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Macro indicators such as population trends and healthcare spending.

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Qualitative trend information and assumptions.

Data is then cross checked by the expert panel.

Expert Panel



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