Development of novel agents for the treatment of hepatitis C virus
Authors: Tracy Swan, Raymond T. Chung
Journal: Hepatology (2008)

As participants in the 2006 Food and Drug Administration meeting on development of novel agents for the treatment of hepatitis C virus (HCV), we were delighted to see the summary of the Committee's recommendations by Sherman and colleagues in the December issue of HEPATOLOGY. We wholeheartedly support registration trials in representative patient populations. There are ethical, practical, and scientific reasons for studying experimental therapies in representative populations. Social justice requires that "…[researchers] should not offer potentially beneficial research only to some patients who are in their favor or select only 'undesirable' persons for risky research."1 In addition, regulators want a representative sample of patients who will be using a drug included in registration trials; patients and clinicians want a realistic idea of safety, efficacy, and tolerability of a given treatment; and sponsors benefit from pursuing a broad indication, because public and private payers are likely to place increasing limits on off-label use. Furthermore, age and population-specific prevalence of HCV in the United States limits the number of treatment-naïve patients with mild to moderate fibrosis in otherwise perfect physical and mental health. The days of cherry-picking trial participants are coming to an end. In particular, patients coinfected with human immunodeficiency virus (HIV) and HCV have urgent need for more effective and less toxic HCV therapies. HCV is a serious and common comorbidity among HIV-positive persons in the United States and Europe; approximately one-third are coinfected with hepatitis C.2, 3 HIV increases both the progression rate and severity of hepatitis C; coinfected people are twice as likely to develop cirrhosis than those with HCV alone, sometimes in less than a decade.4, 5 Although hepatitis C is treatable, regardless of HIV status, the current standard of care—pegylated interferon and ribavirin—is less effective for coinfected people, and the side effects often limit treatment.6, 7 Hepatitis C–associated end-stage liver disease has become a leading cause of death among HIV-positive people in areas where antiretroviral therapy is available.8, 9 In fact, liver-related death is now the most common cause of non–AIDS related mortality among HIV-positive people in the United States and Western Europe.10 It is ironic that we have dramatically altered the prognosis for HIV, which is currently incurable, only to see HIV-positive people dying from complications of hepatitis C, a disease that can be cured. Trials of novel HCV therapies in coinfected persons are usually launched after their approval for treatment of HCV monoinfection. Given the prevalence and severity of HCV disease among HIV-positive people, this delay is now unacceptable. We urge sponsors to initiate drug-drug interaction studies with antiretroviral agents as early as possible, to facilitate prompt initiation of safety and efficacy trials in persons coinfected with HIV/HCV. Ideally, these studies should be launched after completion of Phase IIb studies unless a compelling safety issue has arisen. Tracy Swan*, Raymond T. Chung M.D. , * Hepatitis C/HIV Coinfection Project Director, Treatment Action Group, New York, NY, Associate Professor of Medicine, Harvard Medical School, Director of Hepatology, Medical Director, Liver Transplant Program, Massachusetts General Hospital, Boston, MA.