The Crisis in. Vaccine Development

Transcription

1 The Crisis in Vaccine Development Stanley A. Plotkin 1 Annecy 2015

2 The Evolution of the Vaccine Industry th -19 th Centuries Pioneers National Producers Globalization Innovation but contraction Now Philanthropy and pooled procurement 2

3 Ideas for Vaccines Often come from academic or biotechs Biotechs are privately funded Patents are sought by both Income from those patents often important to survival R&D in these organizations done largely in Europe and North America 3

4 Challenges for Vaccine R&D (1) by Academia and Biotechs Basic discoveries need additional research and development to achieve licensure, plus large clinical studies Increased cost, time and risk of Vaccine R&D driven by Late stage (phase 3) studies and construction of facilities for manufacture: 4

5 Today s Challenges for Vaccine R&D (2) Continuously rising manufacturing standards for new and existing vaccines. Continuously increasing regulatory requirements for existing and new vaccines. The scientific challenge of developing vaccines for unmet needs e.g. RSV, CMV, HIV, TB and Malaria Human Vaccine Project badly needed 5

6 Key Problems in Vaccinology Trans-Vaccinology - Pathogen Variability and Escape - Short Effector Memory - Obtaining the right functional responses - Population Specific Challenges Pathogen- Specific - Uncertain Correlates of Protection - Antigen(s) Required for Protection unknown 6

7 Two Types of Manufacturers Research-Driven Compete through innovation maximizing efficiency but will stop producing old vaccines or move production to Asia Research-Poor Compete through low costs but costs will increase if they want to export 7

8 Estimated Development Costs for a Licensed Vaccine $ Millions Oxfam Merck Rota Sanofi Avg Sanofi Dengue % of projects fail 8

9 Comparative R&D Budgets in the Vaccine Industry Sales (Billion Euros) % Sales GSK % Novartis % Sanofi Pasteur % Serum Inst. India 0.4 2% 9

10 Profit Drives Innovation and Capital Investment Cost of failures Challenging targets : e.g. Dengue Improvement in old vaccines e.g. influenza, pertussis Increasing regulatory demands Can they be reduced by in vitro systems? 10

11 Supply Problems At least two major vaccine manufacturers have exited from the domain: Novartis and Baxter 2 manufacturers announced withdrawal from EU Influenza Market in (Baxter and Crucell) Continuing UNICEF DTP supply crisis as there is a single supplier. (Biopharma Indonesia) Single UNICEF supplier of MR (Serum Institute India) 3 of 4 Yellow Fever vaccine suppliers are unable to produce A single global producer of MenA Conj (SII) for Africa suggests that this is an unattractive market 11

12 The Problem of Minor Vaccines Many infections for which we have no vaccines are relatively restricted and therefore markets are not large. Examples include Ebola, Lyme, MERS, cryptosporidium, West Nile. Major companies will not spend millions of dollars without a certain market. 12

13 Example New Lyme Disease Vaccine: Response to my request to pursue development: GSK - No Merck - No Pfizer - No Sanofi - Maybe Takeda - No 13

14 Innovation Problem WHAT THE MANUFACTURERS BASE DECISIONS ON: Market size Desire of public health authorities Feasibility of development (Is there a Proof of Concept) Competition 14

15 Possible Solutions for Certain Vaccines Government support for development and production Advanced Market Commitment to recommend a vaccine once licensed. FDA/EMA agreement to limit numbers needed for efficacy trials: Phase 2B vs. 3. International Vaccine Development Fund 15

16 Manufacturing Capability May Leave US and Europe In order to reduce costs, particularly of old vaccines. All DTPwc for UNICEF now made in Indonesia 16

17 The Problem: Extraordinary profits cannot be accepted, but how can we strike a balance between profits that drive R&D and price that is affordable for all countries? Quality and Innovation are costly! 17

18 The Free Market Has Given Rise to Tiered Pricing. Source: UNICEF Supply Division, CDC Vaccine Price List 18

19 Today s Vaccines R&D Challenges Price as the dominant metric of vaccination success takes no account of cost of sustaining quality, reliability, innovation and diversity of producers, leading to market failure when significant re-investment is required. 19

20 New Vaccines will be expensive Old Vaccines must be produced with quality We must not strangle invention but rather promote it Answers include increased liaisons between companies in rich and poor countries to facilitate technology transfer Increased spending by governments on health 20

21 A Global Vaccine Development Fund is Needed To Support biotechs through the Valley of Death leading from the lab to proof of concept To support large pharma s efforts to develop vaccines without large markets 21

22 Possible Steps for United States For New Vaccines ACIP/NVAC should create Target Product profile and make Advanced Recommendation Commitment More vaccine research at NIH US Govt/ Donors should make Advanced Market Commitment? $3 billion For Old Vaccines To keep manufacturers in US maintain price to yield small profit 22

23 SUMMARY The Vaccine industry is entering a crisis Research-driven industry is contracting Incentives are needed for industry to invest in vaccines for both major and minor markets Incentives are also needed for improvement of old vaccines 23