An FDA Advisory Committee voted unanimously to endorse FDA approval of sofosbuvir for treatment of chronic HCV. Sofosbuvir is a first-in-class molecule. Significantly increased sustained virologic response (SVR) rates, excellent tolerability, and shortened treatment courses have been observed in clinical trials.
For genotypes 2 and 3, the combination of sofosbuvir and ribavirin represents the first all-oral regimen for treatment of chronic HCV, a truly seminal event in the therapy of this life threatening disease. For the genotype 1 patients, far more common in the United States than genotypes 2 or 3, a course of pegylated interferon-alfa, ribavirin, and sofosbuvir was administered for 12 weeks. SVR rates of 89% were noted in treatment naive patients, significantly higher than any other regimen for treatment-naive genotype 1 patients. Genotype 4 patients (treatment naive) had a 96% SVR rate with this combination.
Fortuitously, there were no significant safety signals identified for sofosbuvir in more than 1,000 patients studied.
Although the addition of sofosbuvir to the armamentarium for treatment of chronic HCV represents a momentous advance, the evolution of therapy for HCV is not over. For genotype 1, this regimen will serve as a placeholder until highly effective interferon free regimens are available, likely within the next year or so. For genotype 3, regimens that offer higher SVR rates with shorter courses will be sought. Studies with interferon-free regimens are underway to provide data on special populations such as HIV-HCV coinfected and pre-and post-liver transplantation populations that represent significant unmet medical needs.
FDA approval of sofosbuvir is a remarkable achievement and is the first step toward the availability of short courses of highly effective and well-tolerated interferon-free medical regimens for patients with chronic HCV. Daunting challenges remain. The new CDC screening recommendations to identify patients with HCV, more than half of whom remain undiagnosed, must be implemented. Strategies must be devised to enlarge the pool of health care providers who treat patients with HCV by providing innovative educational initiatives. Approaches to ensure access for afflicted patients to receive the new expensive regimens will also be paramount.
Dr. Steven Flamm is chief of transplantation hepatology, professor of medicine and surgery, at Northwestern University, Chicago. He is a speaker for Vertex and Gilead; consultant for and has received research support from AbbVie, Vertex, Merck, Janssen, Gilead, and BMS; and he has received research support from Boerhinger-Ingelheim.
