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FDA Hepatitis C Hearing Oct 19, 2006

FDA Hepatitis C Hearing Oct 19, 2006. Jules Levin Executive Director/Founder, NATAP National AIDS Treatment Advocacy Project. Background. NATAP founded 1995 Member of ACTG & HIV RAC Committee for 5 years as NYU/Bellevue community representative 1st Coinfection peg/rbv cure.

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FDA Hepatitis C Hearing Oct 19, 2006

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  1. FDA Hepatitis C Hearing Oct 19, 2006 Jules Levin Executive Director/Founder, NATAP National AIDS Treatment Advocacy Project

  2. Background • NATAP founded 1995 • Member of ACTG & HIV RAC Committee for 5 years as NYU/Bellevue community representative • 1st Coinfection peg/rbv cure. • Worked closely with FDA in 1995 for accelerated protease inhibitor access and approval

  3. NATAP • www.NATAP.org website is a leading resource on HIV, HCV & HBV • Conference Coverage, Journal Publications, News • HIV & Hepatitis Treatment Education; • First HIV education forums 1995 • First coinfection education forums 1999 • National HIV & Hepatitis Education Forums: 25 cities; 15,000 attendees; met with local & national government officials • HCV & HBV coinfection in the Ryan White Care Act

  4. HCV drug development is accelerating We need to speed up drug development process: -- Animal & human safety studies should be accelerated -- Phase I/II should be abbreviated Prevent drug resistance as serial monotherapy in HIV resulted in HIV drug resistance • Multiple Investigational Drug Studies are important in HCV & companies need to collaborate; FDA needs to streamline process • HIV Drug Development Model Fast Track Accelerated Approval for advanced disease Expanded Access

  5. We Need To Improve • End Stage Liver Disease, HCV/HIV coinfection, decompensated cirrhotics are in particular need • Can we accelerate animal & human safety & efficacy study timeline? • Can we start multiple investigational drug studies in phase IIb/III • RESISTANCE, Cross-Resistance; need Resistance Assays & databases • HCV/HIV coinfection is the leading cause of death & hospitalization in HIV (except for AIDS); undetected in developing world • TWO DISEASES: mono-infection & co-infection

  6. Questions • Populations: efficacy/safety studies simultaneous with Phase II/III before approval in needy populations: coinfection, liver transplant, cirrhosis, decompensated cirrhosis • Control arms • Endpoints • Follow-up research

  7. Study Populations • HCV monoinfection • HIV coinfection: PK and efficacy studies conducted before approval • HBV/HCV coinfection • Genotype 1; genotype 2/3; genotype 4 • Cirrhosis • Decompensated cirrhosis • Pre and post liver transplant • Naives • Ethnic/racial groups: African-Americans, Latinos • Null responders • Partial responders • Relapsers • IDUs, Substance Abusers, Alcohol users, Methadone

  8. Endpoints • Primary endpoint SVR: 24 weeks after end of treatment • Secondary endpoint and non-responders: improved liver histology • Durability should be demonstrated with oral agents • Need to look at early responses: 2, 4, 8, 12 weeks

  9. Endpoints • Correlate SVR, biopsy and non-invasive tests although these may not be necessary

  10. Study design • Study reduced dose peginteferon • No ribavirin • No pegIFN • Establish safety and efficacy in humans • Worried about Resistance using old model of adding 1 new oral agent to Peg/RBV?? • Need to study 2 or 3 investigational oral agents in regimen • Switch drug or class if viral failure

  11. Study design • Problem: if VX950 looks good who will want to enroll in new drug studies • Standard of Care will be VX950+Peg/RBV • VX950 + or another PI or potent 4 to 5 log drug in combination with 1 or 2: NM283, R1626, MK0606, HCV-796 • Substitute oral agent for ribavirin • Resistance profiles • SUGGEST: - 7 or 14 day monotherapy depending on resistance potential followed by - Combinations of oral agents with and without Peg & Peg/RBV - Drug-drug interaction studies conducted before combination studies - Coinfection studies

  12. Follow-Up • Although SVR is predictive with Peg/RBV I have concern about oral agents only. I think followup is way to address this concern • 3 yrs SVR follow-up • Long-Term Cohorts: efficacy, liver disease confirmation & safety, cancer, improved histology • Hepatitis C Study Consortium: independent, not NIH nor ACTG • Evaluate low level HCV found in SVRs • We need resistance databases When is the next meeting??

  13. Research Questions • In coinfection, affect on CD4 response to HAART • When to begin HAART & HCV therapy in coinfection; prevent hepatotoxicity • Affect of HCV on metabolics in coifected

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