The Food and Drug Administration’s Antiviral Drugs Advisory Committee met on October 19 and 20 to discuss issues regarding the development and approval of new drugs to treat hepatitis C. A number of investigational drugs – particularly hepatitis C protease and polymerase inhibitors – are far along in development, making the meeting a timely one. Questions examined by the Committee related focused on four broad areas:
1. Identification of appropriate control arms (in clinical trials, people receiving the investigational drug are compared to those in the ‘control arm’, who typically receive the standard of care – pegylated interferon and ribavirin – plus placebo)
2. Populations for study (including whether to include people with all hepatitis C genotypes, people with advanced liver disease, and people co-infected with HIV; the importance of studies in people who have never been previously treated for hepatitis C vs. in people who have prior treatment experience but did not clear the virus; racial/ethnic diversity in study participants; the need for data on new drugs in children and in liver transplant recipients)
3. Endpoints (the measurement of treatment success – for hepatitis C, typically a sustained virologic response [SVR], defined as undetectable viral load six months after the end of treatment; other possible endpoints include normalization of liver enzyme values such as ALTs, and reduction in liver inflammation as measured by biopsy)
4. Long-term follow-up (whether people with an SVR after treatment remain undetectable several years later, and whether successful treatment results in improvements in the liver and reductions in complications of liver disease [such as decompensated cirrhosis and liver cancer])
Jules Levin of NATAP presented a community perspective (online here, or here for PowerPoint file), emphasizing the importance of research new drugs in people co-infected with HIV prior to approval, and the desirability of study designs that allow participants to receive two investigational agents, due to concerns about drug resistance (resistance to new hepatitis C protease and polymerase inhibitors can emerge quickly and compromise treatment success). The Advisory Committee also included two community members and long-time advocates, Tracy Swan of Treatment Action Group and Bob Munk of AIDS InfoNet.
Documents from the meeting, including slides and transcripts, are available online here.
Highlights from the meeting, and other research issues, follow below.