Compound Solutions

1. Compound Solutions Initiatives in new therapies for tuberculosis and malaria Susan Craddock University of Minnesota

2. Between 1975 and 2004, 1556 new chemicals were marketed globally, but only 20 of these, or 1.3%, were for tropical diseases and tuberculosis, even though these account for 12% of global disease burden. (MSF, What is wrong with R&D today?)

3. Factors shaping current drug/vaccine development: • Bayh-Dole Act of 1980 (United States) • EU Biotech Directive of 1988 (Schneider 2009) • WTO’s Trade-Related Aspects of Intellectual Property (TRIPS) 1994, 2001 (Doha Agreement)

5. •Before two years ago there had been no new TB drugs with new targets for over four decades •WHO recommended drug treatment regimen of isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months, then first two for four more months. Complicated regimen that is difficult to complete particularly in areas with inadequate resources •Though all are off-patent, second-line drugs (if above first-line drugs fail) are very expensive because pharmaceutical companies don’t want to manufacture them. •These drugs also have sometimes severe and lasting side effects

6. Source: Donald and van Helden, 2009, with WHO data

7. Product Development Partnerships (PDPs) are nonprofit organizations, pharmaceutical companies, academic researchers, donors such as the Bill and Melinda Gates Foundation and USAID, who collaborate on developing new drugs and vaccines for diseases like tuberculosis.

8. Will these innovative succeed in changing the current landscape of drug research and production? • A. will new therapies result • B. will PDPs create lasting changes in how we think about the relationship between drug or vaccine production and public health need? • C. will new scientific capabilities result from collaborations

9. Why now for PDPs? • The increased visibility that AIDS brought to the issue of making drugs accessible to populations who needed them • More stringent FDA regulations on what drugs or biologics could achieve approval • Many blockbuster drugs were going off-patent and not being replaced with new ones • Pharmas possibly seeing growing markets in low-income countries with growing middle classes

11. TB Alliance: clinical trials featuring drug regimens, not single drugs • Pa-824, Pyrazinamide, Moxifloxacin (PaZM) going into Phase III trials • FDA willing to approve regimens • CPTR: collaboration across pharmaceutical companies

13. ‘The growth of PDPs has electrified the field of infectious disease research, opening the way for getting new compounds into the drug development pipeline for the first time in decades and creating more potential for treatment capacity down the road than existed even a decade ago’ (Casenghi, MSF, 2009).

14. Aeras Headquarters, Rockville MD

15. 3 Belgian Sites Rixensart Wavre Gembloux

16. MVA85A: Phase IIb clinical trial ongoing in HIV+ adults, infants • M72 + AS01E: Phase II trials ongoing • Crucell AD35/Aeras-402: Phase Iib trials in BCG vaccinated infants

18. SATVI, Worcester

22. “What we’re trying to show is that private companies that have a significant vested interest in R&D and intellectual property can also be open-minded enough to try and be a catalyst for change.” • Andrew Witty, CEO, GlaxoSmithKline, 2009

23. Scientifically: • innovative clinical trials, • working across diseases and pharmaceutical companies, • innovative working groups involving the WHO, the FDA and the EMA, etc., • collaborative rather than proprietary approach • Revaluing failure, time, creativity in science

24. “Nothing I’m announcing here involves us giving away huge amounts of money…The point is to ask, can a company try and move this debate off the plateau that I think it’s been stuck on for the last decade” • Andrew Witty, 2009

25. Acknowledgments • Thanks to Jean-Paul Gaudilliere, Lisa Richey, Vinh-Kim Nguyen, Catherine Campbell • NSF Scholars Award grant #SES1027285