Gilead Sciences, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Hepcludex^® (bulevirtide-gmod) 8.5 mg for the treatment of adults living with chronic hepatitis delta virus (HDV) infection, making it the first and only approved treatment for HDV in the United States.

The FDA granted accelerated approval to Hepcludex based on reductions in HDV RNA and normalization of alanine aminotransferase (ALT), supported primarily by data from the pivotal, controlled Phase 3 MYR301 study. At Week 48, the study demonstrated a statistically significant improvement versus the control (delayed treatment) group in a combined virologic and biochemical response. Improvement in disease-related clinical outcomes has not been established. Continued approval for the approved indication may be contingent on verification and description of clinical benefit in a confirmatory trial.

Chronic HDV is considered the most severe form of viral hepatitis and is associated with a markedly higher risk of rapid disease progression, liver failure, and mortality compared with HBV alone. In the United States, studies in general populations have estimated that HDV affects between 2% and 4% of individuals who have chronic hepatitis B virus (HBV), representing ~40,000-80,000 people.

“Hepatitis delta virus is associated with rapid progression of liver disease and a high risk of serious or even life-threatening liver-related complications,” said Dr. Ira Jacobson, MD, Department of Medicine at NYU Grossman School of Medicine. “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.”

MYR301 (NCT03852719) evaluated the efficacy and safety of Hepcludex in adults with chronic HDV, with treatment administered for up to 144 weeks followed by 96 weeks of off-treatment follow-up. Hepcludex met its primary endpoint at Week 48, with continued treatment, demonstrated sustained efficacy and was generally well tolerated through up to 144 weeks of on-treatment exposure.

“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,” said Dietmar Berger, MD, PhD, Chief Medical Officer at Gilead Sciences. “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.”

U.S. Access and Hepcludex Approval Across Markets

The Gilead Support Path^® Program offers information and resources to help patients diagnosed with chronic HBV, HDV and hepatitis C virus (HCV) and primary biliary cholangitis (PBC), as well as healthcare professionals, understand coverage and financial options for prescribed Gilead treatments.

Bulevirtide 2 mg is also approved for use in the European Economic Area (EEA) and other countries globally to treat people living with chronic HDV.

Please see below for U.S. Indication and Important Safety Information for Hepcludex.

U.S. Indication for Hepcludex

Hepcludex (bulevirtide-gmod) 8.5 mg for injection is indicated for the treatment of chronic hepatitis delta virus infection in adults without cirrhosis or with compensated cirrhosis.

This indication is approved under accelerated approval based on a decrease in HDV RNA and alanine aminotransferase (ALT) normalization. An improvement in disease-related clinical outcomes has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

U.S. Important Safety Information for Hepcludex

IMPORTANT SAFETY INFORMATION

BOXED WARNING: POSTTREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS D and B

Severe acute exacerbations of hepatitis D and hepatitis B may occur after HEPCLUDEX is discontinued, especially in patients with cirrhosis, who may be at increased risk of more severe flares or progression to hepatic decompensation. Monitor hepatic function closely with both clinical and laboratory follow-up, including hepatitis B virus (HBV) DNA and hepatitis delta virus (HDV) RNA viral load, for at least six months in patients who discontinue HEPCLUDEX. Resumption of antiviral therapy may be warranted.

Warnings and Precautions

Hypersensitivity reactions including anaphylaxis: Hypersensitivity reactions, including anaphylaxis, have been reported with HEPCLUDEX. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue HEPCLUDEX and initiate appropriate treatment.

Adverse Reactions

Most common adverse reactions (incidence ≥10%; all grades) in HEPCLUDEX clinical trials were injection site reactions, headache, abdominal pain, fatigue and pruritus.

Dosage and Administration

• Dosage in adults: 8.5 mg once daily administered by subcutaneous injection
• HEPCLUDEX should be continued as long as it is associated with a response to treatment. The optimal treatment duration is unknown.
• In all patients, manage the underlying HBV infection as clinically appropriate.

Pregnancy and Lactation

• Pregnancy: There are insufficient data from human pregnancies exposed to HEPCLUDEX to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
• Lactation: There are no data on the presence of HEPCLUDEX in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for HEPCLUDEX and any potential adverse effects on the breastfed child from HEPCLUDEX or from the underlying maternal condition.