the challenge of antibiotic r&d · the challenge of antibiotic r&d john h. rex, md svp...

The Challenge of Antibiotic R&D

John H. Rex, MD SVP & Head of Infection Global Medicines Development, AstraZeneca

Non-Executive Director & Consultant, F2G Pharmaceuticals

[email protected]

Slides happily shared – just drop me a note

Rex JH - 2014-12-09 Stockholm seminar - Challenge of antibiotics 1

mailto:[email protected]

Why so few new drugs?

For today, let’s break it down to four things

Three big problems

1. It’s hard to discover new antibiotics

2. It’s hard to develop new antibiotics

3. The economic value of a new antibiotic to a developer can be close to zero

And the idea that

4. Fixing this requires us to see it as an ecosystem


Agenda

• The 3 big problems

–Discovery is hard

–Development is hard

–Economics are poor

• We must take a systems approach

• Conclusions


Antibiotics are hard to discover

• Easy to find: Targets

– Multiple bacterial genomes are fully sequenced

• Easy to find: Things that kill bacteria

– Bleach works quite well, as do steam and fire

• Hard to find: Kills bacteria & is safe

– Failures: physical properties, pharmacology, safety

– Need high levels to penetrate bug high doses

• Typical lipid-lowering agent: 5-20 mg/day

• Typical antibiotic: 100-2000 mg/day

• And finally, antibiotics are chemically different… Payne DJ et al. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov 2007;6:29-40.


Chemical space: antibiotics vs. other drugs

Other Drugs

Gram-positive antibiotics

Gram-negative antibiotics

Antibiotics vs. Other Drugs

logD (pH 7.4)

• A useful way to think about

chemical similarity and diversity is

to plot molecules based on

• LogD (a measure of water

solubility at a given pH) vs.

• Molecular Weight (MW)

Rex JH - 2014-12-09 Stockholm seminar - Challenge of antibiotics

5 Slide courtesy Matt Cooper & COAD (Community for Open Antimicrobial Discovery)


Other Drugs




logD (pH 7.4)

• Antimicrobials are often very

different from other drugs




Other Drugs




logD (pH 7.4)






Other Drugs




Australian Biotech

Company Commercially-sourced

diverse set

Typical Corporate Libraries

logD (pH 7.4)



• Corporate libraries mostly contain

things that don’t look like antibiotics.

Searching here is not likely to be

productive!



Published Academic

Compounds

This insight can be turned into action

Other Drugs




Australian Biotech

Company Commercially-sourced

diverse set

Typical Corporate Libraries

logD (pH 7.4)

• A program recently funded by the

Wellcome Trust (COAD) will make

testing available to investigators

with compounds

• The goal: new leads in this space



Agenda






• Conclusions


The paradox of resistance

• You might think that resistance would make it easy to develop new antibiotics

• But, it’s actually surprisingly difficult to do this work

• To see why, let’s look at antibiotic development as a series of linked challenges…


You can’t always get what you want

(Rolling Stones)

Development is hard A series of linked challenges

• The superiority-based approaches that work for other areas do not offer a long-term path to a diverse, vibrant antibiotic pipeline

• We have to make non-inferiority (NI) work. How?

– The tiered framework

• The role of (rapid) diagnostics

• Other issues


Trial Design Options: Superiority • Superiority designs are very compelling

– And if dramatic, small is possible: 1/40 vs. 39/40 is credible

• The catch: For superiority in prospective, randomized studies to be a reliable path for antibiotics, randomization to potentially ineffective or toxic therapy must be acceptable1,2

– Remember: Untreated infections are lethal

– Unless we have no choice, must not enroll if the pathogen is resistant and the comparator is thus likely ineffective

– For comparator-susceptible pathogens, modern comparators at full dose are very effective

– Superiority is unlikely and active drugs could be discarded


1Nambiar et al. Clin Pharm Ther 96:147-149, 2014. 2Rex et al. Ann NY Acad Sci doi:10.1111/nyas.12441, 2014.

If clinical superiority is readily achieved, we have a problem

• So, when might you rely on a superiority-based approach?

• Perhaps today (2014) for highly resistant pathogens where a nephrotoxic drug (e.g., colistin) is justified as standard therapy

– Going forward, new drugs should steadily render inferior comparators unethical and superiority trials infeasible

• Related approaches have the same limitation

– Nested superiority in an NI trial?1 Add-on superiority?2

– For both: base therapy must be inadequate (or we must knowingly give inadequate therapy ) for superiority to be reasonably likely


1Huque MF et al. Hierarchical nested trial design for demonstrating treatment efficacy of new antibacterial drugs in patient

populations with emerging antibacterial resistance. Stat Med (wileyonlinelibrary.com)DOI:10.1002/sim.6233, 2014. 2A study of

NEW + OLD vs. placebo + OLD could seek superiority but would only be likely to succeed if OLD was poor.






• Other issues


Trial Design Options: Non-Inferiority

• We generally must instead use this design

– Drug X vs. Drug Y, both at meaningful doses

– Exclude if pathogen is resistant to either agent

– No rational expectation of superiority in this study

• You can still study many resistant pathogens

– E.g., if you use a carbapenem as the comparator, you can enroll any Gram-negative other than a carbapenem-resistant organism

• Problem: The trials tend to be large (700+)

– PK-PD to the rescue…


PK-PD1 & Totality of the Data

17 Rex JH - 2014-12-09 Stockholm seminar - Challenge of antibiotics

PK-PD Index (e.g., AUC:MIC

Ratio)

Eff

ec

t

Emax EC50

MN Dudley, Griffith D. In: Nightingale CH, Murakawa T, Ambrose PG ed. Antimicrobial Pharmacodynamics in Theory and Practice. New York, Marcel Dekker Publishers, 2002.

• Unlike most other drugs…

• Antibiotic blood levels, the

minimum inhibitory concentration

(MIC) of the drug for the bug, and

response have an unusually

predictable relationship

• With rare exceptions,2 blood &

tissue levels that work in a mouse

are very likely to do so in man

1PK-PD = Pharmacokinetic-Pharmacodynamic relationship. See the work of Craig, Drusano, Mouton, Ambrose, Hope, MacGowan,

Nicolau, and many others. 2A classic example is the lack of efficacy of daptomycin in pneumonia that was ultimately found due to the

effects of surfactant on daptomycin (Pertel 2008 CID). 3Peck CC, Rubin DB, Sheiner LB. Hypothesis: a single clinical trial plus causal

evidence of effectiveness is sufficient for drug approval. Clin Pharmacol Ther 2003;73:481-90.

• You still need other data (mostly safety), but PK-PD provides

direct proof of causality that reduces the need for empirical

causality validation3 via multiple trials

Using these ideas, a logical framework can be envisioned


Quantity of Clinical

Efficacy Data that you can

generate

Acceptance of smaller clinical datasets in response to unmet medical need

Rex et al. Lancet Infect Dis

13: 269-75, 2013.

Rex et al. Ann NY Acad Sci

2014, DOI 10.1111/nyas.12441.

Connecting it all: Totality of the Data




generate


Reliance on human PK data combined with preclinical efficacy data


13: 269-75, 2013.


2014, DOI 10.1111/nyas.12441.

Tier A: Our traditional approach


A

P3 x 2



generate


Tier A:

Two big Phase 3 non-inferiority

studies.

Lots of clinical data. Limited reliance on

PK-PD.


13: 269-75, 2013.


2014, DOI 10.1111/nyas.12441.


Tier D: The animal rule


A

D

P3 x 2

Animal rule



generate



13: 269-75, 2013.


2014, DOI 10.1111/nyas.12441.

Tier D:

For biothreats such as anthrax

Human efficacy

trials not possible.

Huge reliance on

PK-PD



And then we add Tier B & Tier C The pathogen-focused pathways


A

B

C

D

P3 x 2

Small studies

Animal rule



generate


P3 x 1 plus small

studies

Pathogen-focused for unmet need



13: 269-75, 2013.


2014, DOI 10.1111/nyas.12441.

Typical Tier B & Tier C Programs1 Good candidate drug for Tier B vs. Tier C

• Tier B: Sufficiently broad spectrum that monotherapy for a syndrome such as intra-abdominal infection is possible

• Tier C: A narrow-spectrum agent that covers but one of many possible pathogens in a syndrome

Phase 3 development program is then

• (Tier B only) Drug X vs. a standard comparator at one body site2 – No (or few) pathogens resistant to the comparator

– PK-PD will provide the link to activity vs. comparator-resistant pathogens

• Resistant pathogen study: Drug X vs. Best Available Therapy (BAT) for highly resistant pathogens for which there is not simple or standard comparator. Prospective, randomized, & open-label. N a few hundred. Multiple body sites.

Rex

JH

- 2

01

4-1

2-0

9 S

tock

ho

lm s

emin

ar -

Ch

alle

nge

of

anti

bio

tics

23 1The example presumes that a clear exposure target is known from preclinical PK-PD and that there is a clear ability to produce a corresponding drug exposure in patients. See literature (Rex et al. Lancet Infect Dis 13: 269-75, 2013) for detailed examples. 2E.g., pneumonia or UTI

These ideas are now mainstream But not yet globally harmonized

• EMA Antibacterial guidance (2013)

– Explicit description of options that match Tiers B & C

• FDA Antibacterial guidance (2013)

– Explicit description of options that match the Tier B ideas

– Unless inferential testing is possible, Tier C is hard for FDA

– We need to work to find flexible ways forward lest important agents not be available in the US

• And also note that antifungal development

– Has effectively long been Tier B-like

– Can now benefit from application of PK-PD ideas

– And are eligible for the US GAIN incentives


We will need to rethink Health Technology Assessor (HTA) & Payor requirements

• Labeling strongly impacts reimbursement

• This is the problem of evidence vs. access1

– Antibiotic data packages will often be small

– We will not routinely generate superiority data (see above)

• But, HTA & Payor analyses prefer larger data packages with a focus on superiority data

• Reimbursement criteria must be adapted

– E.g., Medicare NTAP2 payments to supplement DRGs must recognize this problem for antibiotics


1Woodcock J. Evidence vs. access: Can twenty-first century drug regulation refine the tradeoffs? Clin Pharm Ther

91:378-80, 2012. 2NTAP = New Technology Add-On Payments: The quick adjustment to DRGs made when a new

technology emerges.






• Other issues


1Another example: Take the 50% rate typical of hospital-acquired pneumonia to 75% and the study size shrinks by a third.

Diagnostics increase trial efficiency • In general, we must enroll in a clinical trial before we

have the culture result

– Cultures are often negative (can easily be > 50% rate)

– But, only those subjects with a relevant positive culture contribute fully to analysis of the new drug

• A positive rapid test would serve us well even if it only selected patients more likely to subsequently have a definitive positive culture

– Test might rule in or rule out – doesn’t matter

– If a test moves us from 30 to 50% culture-positive...

– Study size goes down 40%: we save cost & time1


Key test requirement: SPEED • Speed1 & ease of use (local!) really trumps

– Care processes take time (collect sample, send to lab, get report, order a drug, get drug from pharmacy, etc.)

– Too much prior therapy may invalidate the patient’s data for clinical trial purposes

• This is a challenge for test developers

– Developing a test with adequate sensitivity and specificity is surprisingly hard. We don’t (yet) have the tests we need

• New technologies may help

– Direct-from-specimen methods, next-generation sequencing, and evaluation of host (patient) gene responses all hold promise


1Contrast this with HIV or cancer where it is often acceptable and appropriate to take a few days to a few weeks to confirm the diagnosis and decide on a course of treatment.

Diagnostics: The dream

• Longitude Prize 20141

• £10m for “best, rapid, accurate, affordable, point-of-care method for diagnosing bacterial infections on a global scale with universal benefit.”

• Would be great to see it be so simple!


1http://www.longitudeprize.org/. Selected by the British people, the Prize commemorates the 300th anniversary of the 1714 Longitude Act which led to John Harrison’s invention of the reliable shipboard chronometer. The graphics above are from the contest announcement.

http://www.longitudeprize.org/






• Other issues


Interpretive Breakpoints • Interpretive breakpoints are concentrations used

when answering the question “Is it susceptible?”

– E.g., “Organisms inhibited by 1 mg/L are susceptible and infections due to them should respond to usual doses.”

• Problem: Historically, we’ve set breakpoints based on the range of observed MICs1 in the clinical trials

– Isolates with the highest MICs are rare and may well not be seen in the (smaller) Tier B /C programs

– Hence, initial clinical trials are usually inadequate to give full insight into best breakpoints

• We must not constrain breakpoints in this way – we really have to use PK-PD to set breakpoints


1MIC = minimum inhibitory concentration of the drug for the bug in a test tube

Pediatrics

• Focused requirements would speed access

• Example:

– Ceftaroline is a recently registered antibiotic

– Initial1 FDA + EMA pediatric commitments entailed studies of ~750 patients over a 6-year period and at a global cost of > $80m

– Too much, too slow. In addition to PK data by age, safety data requirements need to be reasonable


1The size of the program was subsequently reduced about 50%.

Agenda

• Where are we?






• Conclusions


If we want a diverse, vibrant pipeline…

• We must find ways to fund & incentivize this work – “We can’t make companies do this work … we have to

make them want to do this work”1

• Our answer must address several basic tensions – We want to minimize use of all antibiotics – We want to have new(er) antibiotics available on demand – We want those antibiotics developed before the epidemic

• How can we do this? – Noting that “All models are wrong, but some are useful”2…

– … let’s now look at a model that may be instructive

1Spellberg B. The antibacterial pipeline: Why is it drying up, and what must be done about it? Appendix A in Antibiotic Resistance: Implications

for Global Health and Novel Intervention Strategies: Workshop Summary, Institutes of Medicine, 2010. Accessed online at

http://www.nap.edu/catalog/12925.html on 11 July 2013. 2GEP Box and NR Draper in Empirical Model-Building and Response Surfaces, 1987,

John Wiley & Sons, New York, NY.


http://www.nap.edu/catalog/12925.html

The cost of creating an antibiotic An EU-based analysis

• The typical antibiotic lifecycle can be modeled from start to finish1

• The model allows for failed drugs

• Spend and revenue by year are based on industry average data

• Note the Phase 3 bump in spend

• And then a sales curve: ~10 years of protected sales and then ~10 years of declining sales

-$450

-$300

-$150

$0

$150

$300

Disc. Ph 1-3 On market

5 yr 8 yr 20 years

(Spend) Revenue by year

• Approximate total spend (years 1-13): $600m

• Approximate total sales (next 20 years): $2,500m

• But, we’ve forgotten about NPV!

1Sharma, P. & Towse, A. New drugs to tackle antimicrobial resistance: analysis of EU policy options. OHE website, 2011;

Spellberg et al. Nat Rev Drug Discov 11: 168., 2012 Rex JH - 2014-12-09 Stockholm seminar - Challenge of antibiotics 35

0

25

50

75

100

Year 0 +1 +2 +3 +4 +5 +6 +7 +8 +9 +10

Sidebar: NPV (Net Present Value) How much is an investment worth in today’s terms?

• Cash today is worth more than a promise of cash tomorrow (or in ten years)

• Based on cost of capital, risk, etc., it is typical to discount 10% per year

• The math is the inverse of interest on a loan:

• $100 today = $100; $100 in a year = $90; $100 in two years = $81, etc.a

At 10% per year discount, $100 in 10yrs time is only worth $39 today

• A project’s NPV is calculated by

• Computing sales less costs for each year (Annual Net Cash Flow)

• Each future year’s Cash Flow is discounted to today

• The total across all years is the Net Present Value

• Any NPV > 0 means you’ve created (at least some) value

Before we go

further, we

interrupt this

presentation...

Now, back to the story… Rex JH - 2014-09-06 ICAAC Keynote - New tools & pathways for antibacterials a. Actually, I’ve simplified a bit here – the actual values are $91, $83 … but this simpler way of thinking

about it is close enough for illustrative purposes 36

The very real effects of NPV math

-$450

-$300

-$150

$0

$150

$300

-$450

-$300

-$150

$0

$150

$300


5 yr 8 yr 20 years

(Spend) Revenue by year


5 yr 8 yr 20 years

• Now, consider this in NPV terms

• From the standpoint of year 0 (the

day you decide to start discovery),

the graph below shows spend &

revenue discounted 10%/year

• The line below is the cumulative

NPV

• But in NPV terms, it totals to a loss

of around $50m


Recent US-based analysis: same result • Comprehensive model for drugs for 6 key indications

(ABOM, ABSSSI, CAP, cIAI, cUTI, HAP-VAP)1

• NPV of the new drug always < $40 million

– All 90% confidence intervals on estimate went below zero

• Value to the patient was MUCH higher

– Just based on the value of days of work and life restored, the value to society ranged from $500m to $12 billion

• Thus, these EU- and US-based models show that

– Starting antibacterial R&D is not financially rational, at least not with traditional R&D costs and approaches

– We (society) undervalue these drugs


1Sertkaya A, Eyraud J, Birkenbach A, Franz C, Ackerley N, Overton V, Eastern Research Group. Analytical framework for examining the

value of antibacterial products. Report to US DHHS. http://aspe.hhs.gov/sp/reports/2014/antibacterials/rpt_antibacterials.cfm

That’s a problem we must solve

• To restore vitality to the pipeline and ensure we have the life-saving drugs we will need in the future,

• We have to move these models back into positive territory

And, we’re now doing just that…


Agenda

• Where are we?



–Global leadership

–Public-private partnerships

–Economics

• Conclusions


Global Leadership: A partial list 2003 et seq: IDSA: “Bad Bugs, No Drugs”

17 Sep 2009: (EU) Swedish presidency • “Innovative Incentives for Effective Antibacterials”

7 April 2011: WHO World Health day on AMR • “No action today, no cure tomorrow”

17 Nov 2011: (EU) ND4BB program • PPP for Discovery & Development

2011 forward: (US & EU) FDA & EMA • A steady stream of new guidances

2012: (US) GAIN Act (see subsequent slide)

3-4 Oct 2013: (EU) Chatham House Conference • “Antimicrobial resistance: Incentivizing

Change Towards a Global Solution”

2014: (US) PCAST Report


Public-Private Partnerships In the US: NIAID & BARDA

• NIAID: Antibacterial Resistance Program

– Extensive array of preclinical services

– Phase 1 clinical units

– ARLG (Antibacterial Resistance Leadership Group)

– Modeled on ideas such as I-SPY, master protocols are being considered as a way to provide infrastructure that would support development efforts

• BARDA (Biomedical Advanced Research & Development Authority)

– Several public-private partnerships established to date


In the EU: IMI’s ND4BB program (New Drugs For Bad Bugs)

ND4BB cross topic collaboration and dissemination

Topic 1: COMBACTE a) Enabling

Clinical Collaboration and refining clinical

trial design b) Clinical

Development of GSK1322322

c) Clinical Development of

MEDI4893

Topic 2 : TRANSLOCATION

Research penetration and

efflux Gram-negatives Data Hub and

Learning from R&D experience

Topic 4: Driving re-

investment in R&D and

Responsible use of

Antibiotics

Topic 5: Clinical

development of antibacterial agents for

Gram-negative antibiotic resistant

pathogens

Topic 6: Systemic molecules

against HAIs due to

clinically challenging

Gram-negative pathogens

Call 6

Call 8

Call 9

Call 11

Topic 7: Inhaled

Antibacterials in CF and non-CF BE

Discovery Economics & stewardship

Development

Topic 3 : ENABLE

Discovery & development of

new drugs combatting

Gram–negative infections

Development

ND4BB Information Centre – All data generated is submitted and is accessible to all consortium partners

IMI = Innovative Medicines Initiative

Rex JH - 2014-09-06 ICAAC Keynote - New tools & pathways for antibacterials 43

Example: TRANSLOCATION (Topic 2)

Discovery: Improve understanding of drug penetration into Gram-negatives Efficiency: Use a data center to compile and analyze ND4BB related information Management: holding all together & ensuring best practices / communication

Discovery Efficiency Management

44 44 Rex JH - 2014-12-09 Stockholm seminar - Challenge of antibiotics

And finally, economics In the US…

• 2012: GAIN (part of FDASIA)

– Generate Antibiotic Incentives Now

– Extended exclusivity, priority review, fast track, and a requirement to generate new guidances

• 2014: ADAPT (LPAD), DISARM

– Two more pieces of legislation now in discussion

– ADAPT (LPAD): Further support for streamlining antibacterial development

– DISARM: A fix for the NTAP1 problem


1NTAP = New Technology Add-On Payments: The quick adjustment to DRGs made when a new technology

emerges.

And in the EU… ND4BB Topic 4: The DRIVE-AB Project

• Launch meeting: 6 Oct 2014 • “Driving re-investment in R&D and Responsible use of antibiotics”

• Aim: Address the tension between economics & stewardship – Create a multi-disciplinary, multi-stakeholder community (16 public

partners and 7 private partners from 12 countries) with an in-depth comprehension of challenges of antibiotic development

– Develop evidence-based measures for responsible antibiotic use

– Create implementable options for new commercial models that address the needs of multiple stakeholders

– Validate options through modelling

• We expect DRIVE-AB to explore a broad range of approaches – In particular, we hope to see ways to separate (delink) usage from

reward to the innovator. That is, reward should not be sales-based

– Let’s look at two possible examples...


Two intriguing economic ideas • (Push) Refundable tax credits

– For some percentage (e.g., 50%) of qualified expenses, the company either gets a tax credit (if the company has income) or receives a payment of that amount

– Has immediate impact on NPV while also ensuring the company has “skin in the game” that ensures delivery

• (Pull) Insurance-based approaches

– National acquisition at a fixed, predictable rate (e.g., US buys $100m/year of a new antibiotic for 5 years)

– Annual fee guarantees availability of a certain number of courses of therapy, whether used or not

– We should be pleased to buy but not use the drug, just as we are pleased when our life insurance does not pay off


We’re now tackling the entire model! • The typical antibiotic lifecycle can be

modeled from start to finish1

• The model allows for failed drugs

• Spend and revenue by year are best

on industry average data

• Note the Phase 3 bump in spend

• And then a sales curve: ~10 years of

protected sales and then ~10 years

of declining sales -$450

-$300

-$150

$0

$150

$300


5 yr 8 yr 20 years

• With support from NIAID, BARDA, ND4BB, & others plus

the tiered approach, we are truly taking a systems

approach to this problem

• The Discovery and Development support + the tiered

approach is already having an impact

• Last step: Rethinking value and business models

NIAID, BARDA, ND4BB NIAID, BARDA, ND4BB

The tiered approach

ND4BB & New business models


Agenda

• Where are we?



• Conclusions


Our head is round so that our thinking can change direction

(Francis Picabia)

There’s no time to lose It takes 10-20 years to make a new antibiotic


*Hit to Phase 2 based on novel mechanism AB discovery (GSK) #Based on Paul, et al (2010), Nature Reviews Drug Discovery 9: 203-214.

So few companies are still in the game


Graphic adapted from Kinch MS et al. Drug Discovery Today, July 2014.

Active corporate

anti-bacterial programs

Corporate Entries

Corporate Exits

Over the past 15 years

(1998-2013)

• 14 entries

• 36 exits

I’m pleased to see new

companies emerging in

2014, but we have a lot of

ground to reclaim

30

20

10

0

+4

-4

-8

0

# of

companies

2000 1980 1960 1940 2013

2000 1980 1960 1940 2013

IDSA has set the challenge

52

• Global commitment to develop 10 new systemic antibacterial drugs by 2020 (CID; April 2010)

http://www.idsociety.org/10x20/ Rex JH - 2014-12-09 Stockholm seminar - Challenge of antibiotics

4 oritavancin The Medicines Company, Approved: Aug 6, 2014

4

IDSA has set the challenge

53

• Global commitment to develop 10 new systemic antibacterial drugs by 2020 (CID; April 2010)

http://www.idsociety.org/10x20/ Rex JH - 2014-12-09 Stockholm seminar - Challenge of antibiotics

4 oritavancin The Medicines Company, Approved: Aug 6, 2014

4

These four focus principally

on Gram-positives. Of great

interest, several agents for

Gram-negatives are now

approaching registration.

We must take a systems approach • Collaborative R&D

• Streamlined pathways1,2,3

– By acting quickly to create approaches to describe and manage the uncertainty of small data packages,

– We will provide patients with timely access to urgently needed, life-saving antibiotics, and

– We will avoid the paradoxical situation of being forced in the future to accept even greater degrees of therapeutic uncertainty as antimicrobial resistance progresses

• New economic thinking

– We will fail if we don’t unleash the power of private investment


1Hersh et al., Clinical Infectious Diseases 54:1677, 2012. Among 562 respondents in a 2011 survey of the Emerging Infections Network (EIN), 64% reported using colistin during the previous year and 63% reported caring for a patient with an infection resistant to all available antibacterials. 2Boucher HW et al. Clin Infect Dis 56:1685-94, 2013. 3Rex et al. Lancet Infect Dis 2013; 13: 269-75.

In closing

• The incredibly thin pipeline has many causes

– A path to a diverse, sustainable pipeline must be found

• We’ve made a lot of progress! Thank you!

– Discovery is hard: NIAID, BARDA, ND4BB are opening doors

– Development is hard: Now improved! Tiered framework!

– Economics are poor: Tiered framework; New business models

• There’s still more to do

– But, I think (and to borrow a line from Mr. Churchill), we are now at the end of the beginning


With many thanks to all who are part of these amazing endeavors!

the challenge of antibiotic r&d · the challenge of antibiotic r&d john h. rex, md svp...

Documents