Simply put, hepatitis means inflammation of the liver. Chronic hepatitis C virus (HCV), a blood-borne disease of the liver, is a global health concern. In the United States (U.S.), it affects an estimated 3.9 million people, up to 30 percent of whom will develop cirrhosis and 1 percent to 3 percent of whom will develop liver cancer. There are six genotypes, with genotype 1 being the most common genotype in the U.S., accounting for over 75 percent of HCV cases. Approximately 12 percent of U.S. patients have genotype 2 and 10 percent comprise genotype 3. Genotypes 4, 5, and 6 make up less than 2 percent combined in the U.S.
Historically, treatment for chronic HCV was agonizing, as it involved injectable interferon and oral ribavirin, associated with very low cure rates, undesirable safety profile, poor tolerability and a long duration of therapy. Over the last four years, HCV treatment has undergone a paradigm shift, with the approval of once-daily oral direct-acting antiviral (DAA) regimens, providing sustained virologic response (SVR) of over 95 percent, which is synonymous with cure. The approval of sofosbuvir/velpatasvir (Epclusa®) in 2016 marked the first pangenotypic agent, as a 12-week regimen. Pangenotypic drugs work against all genotypes. These major advancements have led to a trending down in utilization of HCV treatments with fewer patients needing retreatment and have sparked the possibility of eliminating HCV at a national and even global level. Yet, there is still an unmet need. The Holy Grail of HCV research is focused on all-oral, ribavirin-free regimens, shorter duration of therapy and options for DAA treatment failures.
As forecasted in the latest edition of MRx Pipeline, two next-generation pangenotypic HCV agents are expected to be approved in August. Gilead’s investigational sofosbuvir/velpatasvir/voxilaprevir is seeking to become a salvage therapy for prior DAA failures as a 12-week regimen, pangenotypic drug for patients without cirrhosis or with compensated cirrhosis. This agent has received FDA’s Breakthrough Therapy designation for patients with genotype 1 who have failed prior DAA therapy, specifically containing NS5A inhibitors. Breakthrough Therapy designation is given to drugs that can treat a serious or life-threatening condition and preliminary evidence suggests that the drugs may demonstrate substantial improvement over available therapy on a clinically significant endpoint. This designation helps expedite the development and review process. The Gilead product is taken as one tablet once-daily.
Glecaprevir/pibrentasvir, Abbvie’s emerging HCV pipeline drug, may be approved as a shorter eight-week regimen across all genotypes, in non-cirrhotic patients. For patients with genotype 1, it has received Breakthrough Therapy designation for those not cured with prior DAA therapy. This Priority Review product has also been studied in difficult-to-treat populations with high efficacy. An FDA Priority Review designation is given to drugs that offer major advances in treatment, or provide a treatment where none existed. The FDA goal for completing a Priority Review is six months, compared to 10 months for a standard review. Abbvie’s regimen is taken as three tablets once-daily.
This August wave of pangenotypic options for HCV should further drive competition and access in the marketplace. They can lead to a cure in larger populations with shortened durations and treating difficult-to-treat patients, including prior DAA failures. These continued advancements in turn make the quest to achieve national elimination goals a viable possibility against this national epidemic.