The regulatory environment for hepatitis C therapies is approaching an inflection point where decisions about clinical trial design requirements - or the failure to make them - could have a major impact on the development of new therapies.
Faced with a profusion of compounds in the clinic, including several poised to enter Phase III trials, and a complex, evolving medical environment, sponsors are looking to FDA for guidance about the populations they will need to study prior to approval, acceptable efficacy endpoints, and strategies for testing combinations of novel compounds.
FDA also is in a position to settle disagreements among industry, academic scientists and patient advocates over the best ways to ensure that new drugs are made available as quickly as possible for populations with the greatest needs.
Trial design issues are ripe because scientific advances have opened up multiple strategies for attacking HCV and because although the threat is changing, there remains an enormous unmet need to combat it.
Over two dozen compounds are being studied in clinical trials for their potential to supplement or replace either or both elements of the standard two-drug combination of PEG-interferon and ribavirin (see "HCV Immunotherapeutics," A2 & "HCV Antivirals," A3).
FDA put the opportunities for new approaches on the table last month, when its Antiviral Products Advisory Committee met to review HCV trial design issues. The two day meeting aired the latest thinking on study populations, how to deal with co-infection, the proper endpoints, ways to speed up trials, and the prospect for fundamental shifts in clinical experiments posed by novel agents (see Online Links, A20).
Industry and academic scientists identified three important results of the meeting: recommending pre-approval studies in special populations, encouraging early small molecule combination trials, and clear definitions of subcategories of the non-responder population.
But a roadmap requires clear FDA guidance, which the agency has not started and, once work gets under way, could take more than a year to produce.
Much of the debate over appropriate requirements for HCV drugs reflects the last two decades of experience with HIV. There is widespread agreement that, like HIV, HCV will be best treated with cocktails that minimize the virus' opportunities to evolve drug resistance.