FDA Approves Hepcludex, First U.S. Treatment for Chronic Hepatitis Delta

The U.S. Food and Drug Administration on Friday approved Hepcludex, the first FDA-approved treatment for chronic hepatitis delta virus infection in the United States, clearing the drug for adults without cirrhosis or with compensated cirrhosis.

The newly approved injection, also known as bulevirtide-gmod, is made by Gilead Sciences Inc. The decision is a notable milestone for a small but high-risk group of patients with a disease the FDA describes as serious and life-threatening. Chronic hepatitis delta can drive rapid liver fibrosis and lead to liver cancer, liver failure and death, yet until now patients had no FDA-approved therapy.

“Today’s approval fills a critical gap in care for patients with chronic HDV infection, who until now have had no FDA-approved therapies available,” Wendy Carter, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, said in the agency’s May 22 announcement.

The approval was based on results from the Phase 3 MYR301 trial, a multicenter, randomized, open-label, parallel-arm study. The FDA said the trial’s main measure of effectiveness was a combined response at 48 weeks: patients had to show either undetectable HDV RNA, meaning the virus could not be detected in blood, or at least a 2 log10 IU/mL decline from baseline, along with normalization of ALT, a liver enzyme used as a marker of liver inflammation.

By that measure, 48% of patients in the immediate-treatment Hepcludex group met the endpoint at week 48, compared with 2% in the delayed-treatment group, according to the FDA. The agency also said undetectable HDV RNA was reached in 20% of treated patients and in none of the delayed-treatment patients at week 48. In the Hepcludex group, that figure rose to 36% at week 96 and 50% at week 144.

The FDA granted the product Breakthrough Therapy designation, Orphan Drug designation and Priority Review, and approved it under the agency’s accelerated approval pathway. That route allows the FDA to clear drugs for serious conditions based on trial measures that are reasonably likely to predict clinical benefit, rather than waiting for longer-term outcomes such as fewer cases of liver failure or death.

The label includes a boxed warning that stopping Hepcludex may cause severe acute exacerbations of both HDV and hepatitis B virus infection. The FDA said possible adverse reactions include hypersensitivity reactions, including anaphylaxis, injection-site reactions, headache, abdominal pain, fatigue and pruritus, or itching.

Hepatitis delta is an unusual liver infection because it occurs only in people who already have hepatitis B virus infection. That means prevention depends on preventing hepatitis B in the first place. The FDA said hepatitis B vaccination protects against HBV and therefore against HDV as well.