Hepcludex (bulevirtide-gmod): FDA approval, pivotal trial and safety
Approved
Type
Therapeutic biologic · Powder,for solution
FDA-approved use
To treat chronic hepatitis delta virus infection in adults without cirrhosis or with compensated cirrhosisWording from FDA's list of novel approvals.
FDA review
Priority reviewOrphan drug
Company
Gilead Sciences
Application
BLA 761468
Specialty
Infectious Disease
Boxed warning: Posttreatment severe acute exacerbation of hepatitis D and B
At a glance
Hepcludex (bulevirtide-gmod) is an entry inhibitor approved by the FDA on May 22, 2026 for chronic hepatitis delta virus infection in adults without cirrhosis or with compensated cirrhosis. Approval is accelerated and rests on HDV RNA decline and ALT normalization. In the phase 3 MYR301 trial, the combined response at Week 48 was 48% with immediate treatment versus 2% with delayed treatment. The boxed warning covers severe hepatitis D and B flares after the drug is stopped.
What it is and how it works
Bulevirtide is a synthetic lipopeptide derived from the preS1 domain of the hepatitis B surface protein. It binds the NTCP receptor on hepatocytes and blocks HDV attachment, so the virus cannot enter liver cells. It acts on viral entry rather than modulating the immune response, which is how interferon-based treatment works. Clinical benefit on disease outcomes has not yet been established.
Multicenter, randomized, open-label, parallel-arm phase 3 trial. Randomization was stratified by compensated cirrhosis. Treatment lasted 144 weeks, followed by 96 weeks of follow-up. The published trial had two bulevirtide dose groups; the label describes the approved dose group versus delayed treatment.
Patients
Adults with chronic hepatitis D, with or without compensated cirrhosis. The published trial enrolled 150 patients (49, 50 and 51 per group). Label efficacy data cover 50 immediate-treatment and 51 delayed-treatment patients. Mean age was 41 years and 48% had compensated cirrhosis.
Compared with
Delayed treatment: 48 weeks of observation with no HDV treatment, then bulevirtide for 96 weeks.
Primary endpoint
Combined response at Week 48: undetectable HDV RNA or a decline of at least 2 log10 IU/mL from baseline, plus ALT normalization.
Result
Combined response occurred in 48% with the approved dose versus 2% with delayed treatment (rate difference 46%, 96% CI 31% to 61%; P<0.0001). In the publication, the lower-dose group had 45% (P<0.001 versus control).
Other results
Virologic response at Week 48 was 76% versus 4%. ALT normalization was 56% versus 12%. Undetectable HDV RNA was 20% versus 0%, rising to 36% at Week 96 and 50% at Week 144 with immediate treatment. Combined response was 54% at Week 144. After treatment ended, combined response was 24% in both groups at posttreatment Week 96. No bulevirtide patient lost HBsAg or had a 1 log10 HBsAg decline by Week 48. Patient-reported outcomes (P3) showed some quality-of-life gains in the lower-dose group versus controls.
Safety in the trial
Injection site reactions occurred in 30% and headache in 20% with treatment, versus none in the delayed group. Publication-reported excess events included pruritus, fatigue, eosinophilia, upper abdominal pain, arthralgia and asthenia. No treatment-related serious adverse events occurred. Bile acid levels rose in a dose-dependent manner.
How does Hepcludex (bulevirtide-gmod) compare with the alternatives (Peginterferon alfa, Nucleos(t)ide analogs (tenofovir, entecavir), Liver transplantation) for chronic hepatitis delta virus infection in adults without cirrhosis or with compensated cirrhosis? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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The boxed warning describes severe acute exacerbations of hepatitis D and B after discontinuation, with higher risk of severe flares or hepatic decompensation in patients with cirrhosis. Hepatic function, HBV DNA and HDV RNA should be monitored for at least six months after stopping, and antiviral therapy may need to be resumed. Hypersensitivity reactions, including anaphylaxis, have been reported, and the drug should be stopped if they occur. The most common adverse reactions (10% or more) were injection site reactions, headache, abdominal pain, fatigue and pruritus. In MYR301 no participant stopped treatment for an adverse reaction through Week 48.
What it competes with
Before this approval, no drug was FDA-approved for chronic hepatitis D. Care centered on controlling the underlying hepatitis B and, in some patients, off-label interferon.
Peginterferon alfaUsed off-label for hepatitis D. Response is limited and tolerability can be poor. It is unsuitable in decompensated disease.
Nucleos(t)ide analogs (tenofovir, entecavir)Suppress HBV, the helper virus, and are often continued alongside other therapy. They have little direct effect on HDV.
Liver transplantationReserved for decompensated cirrhosis or hepatocellular carcinoma in advanced disease.
Bottom line for clinicians
Hepcludex offers the first FDA-approved targeted option for adults with chronic HDV infection, including those with compensated cirrhosis. Approval is accelerated, so benefit on clinical outcomes still needs confirmation. Weigh the durability of response after stopping and the flare risk on discontinuation, especially in cirrhosis, and plan for long-term treatment with close post-treatment monitoring.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 28, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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