Development of drugs in public-private partnership (PPP)

environments

Marija Mavar Haramija / Nathaniel Stanley / Pascal Maugeri

April 2011

 MSc Bioinfo - Computer Assisted Drug Discovery

Agenda15-min slides + 10-min debate

• Introduction• The Old Method• The Challenges of Orphan Diseases• The Public-Private Partnership model• Debate• References

Introduction

• Process of introducing new drugs in the market is expensive, long, and risky• Drug makers only have incentive to introduce drugs to markets where

customers can pay development costs• Most of the resources and experience in drug discovery are held by the

private sector• 90% of the world's diseases receive only 10% of the resources, leading many

of those diseases neglected, or "orphaned"• Public-Private partnerships (PPPs) could allow for some of these diseases to

receive the attention they need while.

The Old MethodA long and costly process

• Traditional drug discovery usually involves exclusively private sector companies. Occasionally they work together, but this is a "simple" process for them.

 • The process of introducing a new drug in the market is usually 10-15 years

long • Huge investment required: average is $868 million but the range is $500-

$2.000 million depending on company strategy and therapy targeted 

The Old MethodA long and costly process

The Old MethodA long and costly process

• "Slowing pace of new drugs coming out of the [US] pharmaceutical industry" (New York Times, Jan. 22, 2011)

• Large drug makers are reducing their R&D spending

• Waves of acquisitions of small biotech companies to temporarily fill in the gap of patents expiry

• Dubious tactics focused on taking advantage of the legal/patent system and drug approval process to extend monopolies on drugs (CBS news article, 12 Jul. 2001)

Orphan DiseasesDefinition and some facts

• "orphan" or "neglected" or "tropical diseases" or "diseases of poor" • A disease which has not been "adopted" by the pharmaceutical industry

because it provides little financial incentive for the private sector to make and market new medications to treat or prevent it.

 • Diseases that:

o affect small number of patients in developed countrieso affect many patients in developing countries, but because they

are unable to pay, drug developers don't invest in that market

• Orphan Diseases = Rare Diseases + Neglected Diseases (EURORDIS)

• EURORDIS estimates the existence of 5000-7000 Orphan Diseases and Orphanet references 5954 diseases (April 2011)

Orphan DiseasesThe Challenges

• 80% of rare diseases have identified genetic originso Cystic fibrosis, Turner sindrome, Huntington disease, muscular

distrophy  • most of neglected diseases are tropical infections 

o  trypanosomal parasites (African sleeping sickness..), bacterial and viral infections (cholera, yellow fever...)

• only 10% of global R&D resources are directed at diseases accounting for 90% of the global disease burden

• existing regulatory incentives (tax incentives, market exclusivity...) may no longer apply

 

Orphan DiseasesSome examples

Malaria (ORPHA673, Prev.: 1-9 / 100 000)• 247 million cases / year according to WHO• 881 000 deaths in 2006 and could double in the next 20 years,

91% were in Africa and 85% were of children under 5 years of age• "In the case of malaria, the immediate problem is drug resistance"

Tuberculosis (ORPHA3389, Prev.: 1-5 / 10 000)• world wide distribution is not uniform: 80% of the population in

many Asian and African countries, 5–10% of the US population• 2007: 13.7 million chronic active cases, 9.3 million new cases, and

1.8 million deaths, mostly in developing countries

Cholera (ORPHA173, Prev.: 1-9 / 1 000 000)• 2010: affects 3-5 million people and causes 100,000-130,000 deaths a year • one of the earliest infections to be studied by epidemiological methods.

Public-Private Partnershipsa complementary collaboration

Public sector

• has a great interest in stimulating discoveries

• knowledge of multiple diseases• links to governments• strong networks in disease-endemic

countries• has not developed its own drug

development infrastructure  

Private sector• strong R&D expertise, marketing, PM,

and regulatory affairs • seeks new therapies by converting

basic scientific discoveries• development of biotech companies

brought high degree of specialization• has disengaged since '70s from

tropical diseases R&D.• "a culture of controlling

R&D collaboration"

Public-Private PartnershipsStructure

• Fundingo private sources, government, international, philantropic and charitable

foundations• Goals

o discovery and development of new drugs for orphan diseaseso improvement of characteristics of existing drugs (to achieve low cost,

easy administration, quick effect, to overcome resistance...)• Large organizations

o UNDP/World Bank/UNICEF/WHO Special Programme for Research and Training in Tropical Diseases (TDR)

• Small organizationso  Medicines for Malaria Venture (MMV)o  Global Alliance for Tuberculosis Drug Development (GATB)o  Drugs for Neglected Diseases Initiative (DNDi)o  Institute for One World Health (IOWH) 

Public-Private PartnershipsAdvantages

• reduces cost on technology, staff, access to compound libraries, etc.

• expertise can be shared

• "The administration of a portfolio of projects offers advantages both scientifically and administratively"

• flexibility: projects may be started at facilities (university and/or company) that have the knowledge or materials

• develop long-term relationships between entities

Public-Private PartnershipsDisadvantages

• Overhead of having distributed workforce• Strong management is required: not easy to manage projects in different

locations across different cultures and timezone• Potential for lawsuits over intellectual property the further along partnerships

go, with which private companies have much more experience

Public-Private PartnershipsIssues

• duplication of efforts among teams• "many PPPs are still in their infancy and are themselves social experiments"

• "scientists in developing countries do not want to be just ‘testers and developers’ of other people’s products."

• "To ensure the long-term sustainability of these programmes, greater involvement of disease-endemic countries has to be built into the PPP model"

• unclear who owns Intellectual Property Rights

Example of PPP Bayer's initiative: Grants4Targets

Grants4Targets allows public researchers to apply for research grants from Bayer Healthcare• Applicants apply for grants via the Grants4Targets website using a standard

format application.• A committee of researchers at Bayer then decide on the proposal• Grants are decide in as little as 8 weeks• Grants come in three sizes, ranging from €5K-250K. Up to €125K, no IP

discussions are necessary, applicant keeps IP.

Example of PPP Bayer's initiative: Grants4Targets

Advantages:• Works well for very early stage development• Low bureaucratic hurdles• Not very complex and "no-strings-attached" IP rights• Potential for future collaboration

Disadvantages:• No strong collaboration• Over 70% of requested grants are for Cancer or Heart disease, NOT orphan

diseases• Only applicable to the very first stages of development

Snapshot of Grants4Targets project after 3 rounds

By percentage, in what fields grants have been requested

Debate

1. How do you feel about this model? Are you convinced that this kind of partnership will be successful?

2. Is private industry benefitting more than they are contributing, or vice versa?3. Do you see any potential problems that could come from disputes over

intellectual property rights? How are we certain drugs will be made available for a reasonable price to those in need?

Referencessome additional reading 

Nwaka S, Ridley R. Virtual drug discovery and development for neglected diseases through public-private partnerships. Nat Rev Drug Discov. 2003:2.

Christopher P. Adams and Van V. Brantner. Estimating The Cost Of New Drug Development: Is It Really $802 Million? Health Affairs, 25, no.2 (2006):420-428

Monika Lessl et al. Grants4Targets – an innovative approach to translate ideas from basic research into novel drugs. Drug Discovery Today. Volume 16, Numbers 7/8, April 2011

Harrris, Gardiner. "Federal Research Center Will Help Develop Medicines" The New York Times. 22 Jan. 2011.http://www.nytimes.com/2011/01/23/health/policy/23drug.html

"Why Do Generic Prescription Drugs Take So Long to Hit the Market?" CBS News. 12 Jul 2001.http://www.cbsnews.com/stories/2002/01/31/health/main327667.shtml

World Health Organization. World Malaria Report. 2008http://whqlibdoc.who.int/publications/2008/9789241563697_eng.pdf

  

Backup slides

New Drugs market entryby disorder and primary indication

Source: Christopher P. Adams and Van V. Brantner. Estimating The Cost Of New Drug Development: Is It Really $802 Million? Health Affairs, 25, no.2 (2006):420-428

The example of MalariaWHO Malaria Report 2008

Estimated incidence of malaria per 1000 population, 2006

Grants 4 TargetsDistribution of applications received

National distribution of applications received, (RoW, Rest of the World)