Gilead Sciences announced that the U.S. Food and Drug Administration (FDA) granted accelerated approval to Hepcludex (bulevirtide-gmod) 8.5 mg for the treatment of adults living with chronic hepatitis delta virus (HDV) infection. The approval makes Hepcludex the first and only FDA-approved treatment for chronic HDV in the United States.
Chronic HDV is considered the most severe form of viral hepatitis because it is associated with rapid progression toward liver failure and liver-related death. In the U.S., HDV is estimated to affect approximately 40,000 to 80,000 people living with chronic hepatitis B virus (HBV).
The FDA’s accelerated approval was based on reductions in HDV RNA and normalization of alanine aminotransferase (ALT), supported primarily by results from the pivotal Phase 3 MYR301 study. At Week 48, Hepcludex demonstrated a statistically significant improvement versus the delayed-treatment control group in a combined virologic and biochemical response. Continued approval may depend on verification and confirmation of clinical benefit in a confirmatory trial.
The MYR301 study evaluated the efficacy and safety of Hepcludex in adults with chronic HDV for up to 144 weeks of treatment followed by 96 weeks of off-treatment follow-up. According to Gilead, Hepcludex met its primary endpoint at Week 48 and showed sustained efficacy with generally favorable tolerability through long-term treatment exposure.
Hepcludex is indicated for adults with chronic HDV infection without cirrhosis or with compensated cirrhosis. The therapy is administered as a once-daily 8.5 mg subcutaneous injection.
The FDA approval includes a boxed warning regarding severe acute exacerbations of hepatitis D and hepatitis B after discontinuation of treatment. Common adverse reactions observed in clinical trials included injection site reactions, headache, abdominal pain, fatigue, and pruritus.
Hepcludex is a first-in-class entry inhibitor designed to block the entry of both HDV and HBV into liver cells, targeting a key step in the viral lifecycle. The therapy is already approved in the European Economic Area and several other global markets in a 2 mg formulation.
Gilead noted that it has already initiated a confirmatory long-term outcomes study as part of the FDA accelerated approval requirements.
KEY QUOTES:
“Hepatitis delta virus is associated with rapid progression of liver disease and a high risk of serious or even life-threatening liver-related complications. For patients, an HDV diagnosis means managing two distinct viral liver diseases—hepatitis B and hepatitis D—each contributing to disease progression, monitoring demands, and treatment complexities. The approval of Hepcludex for chronic HDV represents a critical advancement, introducing a long-awaited option that begins to address a significant unmet medical need and has the potential to meaningfully alter the course of this devastating disease for people living with HDV in the United States.”
Dr. Ira Jacobson, MD, Department of Medicine at NYU Grossman School of Medicine
“The approval of Hepcludex represents a historic milestone for people living with HDV in the United States, marking the first FDA-approved treatment for HDV. This reflects years of close engagement with the FDA and the application of rigorous science to address a serious disease with long-standing unmet need. With Hepcludex, we now have the opportunity to deliver a meaningful clinical advancement that has the potential to change the trajectory of HDV for patients in the U.S.”
Dietmar Berger, MD, PhD, Chief Medical Officer at Gilead Sciences
