Accelerating the search for an AIDS vaccine -- Strengthening regulatory processes

1. Accelerating the search for an AIDS vaccine -- Strengthening regulatory processes Robert Hecht Senior Vice President, Public Policy International AIDS Vaccine Initiative

2. Outline • Why are AIDS vaccines and other new preventive technologies important in the fight against AIDS? • What role does clinical research play, and why is the developing world central to this effort? • How does strengthening processes for trial review help speed the search for a vaccine? • What is IAVI doing to strengthen clinical trial review, and what are we planning to do in the future?

3. Outline • Why are AIDS vaccines and other new preventive technologies important in the fight against AIDS? • What role does clinical research play, and why is the developing world central to this effort? • How does strengthening processes for trial review help speed the search for a vaccine? • What is IAVI doing to strengthen clinical trial review, and what are we planning to do in the future?

4. The world needs an AIDS vaccine Over 1.6 million people are infected with HIV in Latin America, and one-third live in Brazil Worldwide, more than 35 million infected, and 11,000 new HIV infections each day • A comprehensive response: • Deliver for today – better use of tools • Prevent further spread of the virus • Treat those already infected • Mitigate social impacts • Develop better tools for tomorrow • Invest in innovation for new technologies Better prevention – particularly AIDS vaccines – is critical for the affordability and sustainability of our commitments to universal access Source: UNAIDS 2006 Photos: WHO/UNAIDS

5. Ultimately, a vaccine offers the best hope of ending the epidemic New adult HIV infections in low- and middle-income countries by year and vaccine scenario

6. Ultimately, a vaccine offers the best hope of ending the epidemic New adult HIV infections in low- and middle-income countries by year and vaccine scenario 17 million new infections averted

7. Political commitment to new prevention technologies is growing – Toronto August 2006 The quest for [an HIV] vaccine is the single most important quest in the world.– Bill Clinton We want to call on everyone…around the world to help speed up…the discovery of a microbicide or an oral prevention drug that can block the transmission of HIV. – Bill Gates Top priority is to immediately double funding for microbicide research and development. – Peter Piot

8. Political commitment from developing countries is growing – Brasilia September 2006 • “The Heads of State…also committed themselves to further enhancing trilateral cooperation in the field of HIV/AIDS…and to explore the possibilities of concluding a trilateral instrument for collaboration.. for research and development of AIDS, malaria and tuberculosis diagnostic tools, drugs and vaccines” – India, Brazil, S. Africa

9. Outline • Why are AIDS vaccines and other new preventive technologies important in the fight against AIDS? • What role does clinical research play, and why is the developing world central to this effort? • How does strengthening processes for trial review help speed the search for a vaccine? • What is IAVI doing to strengthen clinical trial review, and what are we planning to do in the future?

10. AIDS prevention research is receiving more emphasis, with some results expected in the next couple of years.. Source: Gita Ramjee presenting at IAS Aug 2006

11. …and the developing world is playing an important role Source: Gita Ramjee presenting at IAS Aug 2006

12. …and the developing world is playing an important role Source: Gita Ramjee presenting at IAS Aug 2006

13. …and the developing world is playing an important role Source: Gita Ramjee presenting at IAS Aug 2006

14. …and the developing world is playing an increasingly important role Adults and children living with HIV, 2005 The effort to test and deliver new preventive technologies is particularly important in countries where HIV is most prevalent and these products most urgently needed. Source: UNAIDS 2005

15. 23 countries are conducting AIDS vaccine trials today

16. IAVI Collaborator Sites in Africa and India = IAVI Field Office IAVI India Pune-NARI, India Kangemi and KNH-KAVI, Kenya Chennai-TRC, India Entebbe-MRC, Uganda IAVI East Africa Masaka-MRC, Uganda Kilifi-CGMRC, Kenya Kigali-PSF, Rwanda Lusaka-ZERHP, Zambia Medunsa, South Africa Cape Town-DTHC, South Africa IAVI Southern Africa Soweto, South Africa

17. Many new trials are likely to begin Expected to enter trials Ad 35 NIH-VRC Ad 35 IAVI-Crucell Chimp Adeno IAVI-GSK Chimeric Adeno Harvard-Crucell VSV Wyeth Measles GSK MVA SAAVI; WRAIR AAV-1 IAVI-CRI-TGEN • In preclinical development • Chimeric Adeno Vectors • BCG • VSV • Ad-11 Vector • Pox: NYVAC, MVA • Low sero-prevalent AAV • Reovirus • Newcastle Disease • HIV/VEE Chimeras • HIV/VSV Chimeras • Sendai • CMV

18. And financial commitment to HIV vaccine R&D is growing Public investments in HIV vaccine R&D Source: HIV Vaccines and Microbicides Resource Tracking Working Group, 2006

19. Brazil is a key player in the global search for a vaccine • Historic commitment to public health • Outstanding government AIDS program • Comprehensive approach to AIDS • Highly engaged communities • Sophisticated scientific community • Involvement in AIDS vaccines since early 90’s • Vaccine manufacturing and delivery capacity • Regional and international influence in vaccines and in AIDS generally

20. RORAIMA RORAIMA (1) (1) Vaccine trial sites in operation and under development Potential phase 3 sites (starting epidemiological and socio-behavioral characterization) Cohort in Belo Horizonte (former WHO seroincidence study) Phase 1/2 HVTN sites in Rio and Sao Paulo (international multicentric studies) Source: C. Possas, National STD-AIDS Program

21. Outline • Why are AIDS vaccines and other new preventive technologies important in the fight against AIDS? • What role does clinical research play, and why is the developing world central to this effort? • How does strengthening processes for trial review help speed the search for a vaccine? • What is IAVI doing to strengthen clinical trial review, and what are we planning to do in the future?

22. Intensified research can be enhanced by strong trial review processes • Improving, streamlining trial approval is critical for: • Ensuring that candidates are evaluated among populations that require a vaccine most urgently • Making a safe, effective vaccine available rapidly, but with uncompromised quality of review • Allowing multi-centric research studies in more than one country • Ensuring that communities and trial participants are fully informed and benefit from trials • Developing capacity for approval and registration of new vaccines • Empowering developing countries to weigh risks and benefits based on their own goals and values. Increased speed and efficiency are critical, but countries must retain research independence and capacity to engage in high-quality review.

23. Approval times for AIDS vaccine trials have varied

24. Outline • Why are AIDS vaccines and other new preventive technologies important in the fight against AIDS? • What role does clinical research play, and why is the developing world central to this effort? • How does strengthening processes for trial review help speed the search for a vaccine? • What is IAVI doing to strengthen clinical trial review, and what are we planning to do in the future?

25. IAVI’s work on clinical trial review • Purpose: Facilitate country-led efforts to strengthen trial review systems • Generate data: characterize and describe ethical and regulatory review systems for AIDS vaccine clinical trials • Generate data: document recent changes and improvements in regulatory systems – best practices • Set the stage for more detailed country-led analysis of trials review systems and processes • Encourage national institutions, with support from relevant global organizations, to develop and implement improvements.

26. Brazil • Clinical Trial Review in Brazil • Well-defined clinical trial review system, backed by legislative framework – strong initial framework • Time required for AIDS vaccine trial approval has varied from one month to about nine months • HIV vaccine trials as of June 06: 6 • CEP: institutional ethics committee • CONEP: National Committee of Ethics in Research • ANVISA: national regulatory authority • CTNBio: Brazil technical committee on biosafety • Trials involving GMOs

27. India • Clinical Trial Review in India • Regulations covering clinical trials were revised in January 2005 • A project is now under way to integrate and streamline the process further • Approval took 6 months for first trial and 12 months for the second • HIV vaccine trials as of June 06: 2 • CECHR: Central Ethics Committee on Human Research • Trials of national importance and sensitivity (e.g. HIV vaccine trials) • DCGI: Drugs Controller General of India • RCGM: Review Committee on Genetic Manipulation • Trials involving GMOs • GEAC: Genetic Engineering Advisory Committee • Trials involving foreign products • HMSC: Health Ministry’s Screening Committee • Trials involving foreign collaboration

28. Kenya • Clinical Trial Review in Kenya • New National Guidelines for Research and Development of HIV/AIDS Vaccines developed in 2005 • HIV Vaccine Subcommittee of the Ministry of Health advises and guides review process for HIV vaccine trials • HIV vaccine trialsas of June 06: 5 • PPB: Pharmacy and Poisons Board • NCST: National Council of Science and Technology

29. South Africa • Clinical Trial Review in South Africa • Regulatory review system incorporates peer review by an external committee of scientific and medical experts • MCC is currently taking the lead within the Southern African Development Community (SADC) to develop improved guidelines for clinical evaluation of AIDS vaccines • HIV vaccine trials as of June 06: 5 • MCC: Medicines Control Council • CTC: Clinical Trials Committee of MCC • NDA: National Department of Agriculture • Trials involving GMOs

30. Uganda • Clinical Trial Review in Uganda • Uganda launched Africa’s first AIDS vaccine trial in 1999 • Government has worked to streamline and improve mechanism since then • New Guidelines for AIDS Vaccine Research released in 2006 • HIV vaccine trials as of June 06: 4 • UNCST: Uganda National Council of Science and Technology • NDA: National Drug Authority

31. Key findings across the five countries • No simple common structure and flow • Some reviews in parallel, some in sequence • Many potential bottlenecks • In many cases, there is a need for • Improved communications between trial sponsors and review bodies • Expanded funding and human resource capacity of regulatory bodies • Initiatives to create national HIV vaccine guidelines could improve quality and speed of trials reviews • Greater harmonization among countries could enhance multi-centric trials, and in the long run, licensure of an AIDS vaccine. • Global programs such as the WHO’s DCVR Network, and support from EMEA/FDA, could accelerate access to specialized knowledge and training

32. Next steps • Additional work to support national teams in analyzing trial review processes in depth, in 6-8 countries • Results could be used to: • Provide input to national consultations • Design capacity building programs • Facilitate exchange of information and collaboration between regulatory agencies, including the IBSA countries; • IAVI is ready to work with our national and international partners