1. VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE ALVAC-vCP1521 plus AIDSVAX B/E CRF01_AE (Clade E) -based HIV vaccines Phase 3 Trial in Thailand Sponsor: Office of the Surgeon General, U.S. Army Joseph Toerner, M.D., M.P.H.: FDA, CBER September 23, 2004

2. PHASE 3 TRIAL IN THAILAND ALVAC vCP1521 prime plus AIDSVAX B/E boost in Thai young adults Differing scientific opinions –For example, Science 2004 vol. 303, 305 Purpose of today’s VRBPAC is to provide an update on the ongoing study for committee members –Decision to allow trial to proceed under US IND –Regulatory challenges

3. HIV GENETIC DIVERSITY Complicated global diversity –Clades: short sequences of env –New circulating recombinants identified –Recharacterization of clades (Clade E) Potential obstacle HIV vaccine dev. –Superinfection with different clade HIV NEJM 2002;347:731-6 –Broad immunological responses? –How much cross-clade recognition? Much of HIV vaccine development is clade-specific

5. Vaccine Development, GCP & the Global Challenge Jesse L. Goodman, MD, MPH Director, Center for Biologics Evaluation and Research (CBER) US FDA Presentation to the 2004 ICDRA Madrid, Spain

6. HIV Vaccine: Interesting Issues Is US approval possible for an HIV vaccine that incorporates only non-US prevalent clades? What about any approval of a vaccine of limited efficacy (what do we think of 10 v. 20 v. 40 v. 60 v 80% v. 90+ % condoms)? –Behavioral issues, risks to pt and contacts? –High vs. low incidence areas –Actions based on interim analyses? Would the “right” response differ between high/low risk areas?