Drug Update · Gastroenterology

FDA Approves bulevirtide for chronic HDV: 48% combined response at Week 48

September 01, 2026

Approval date

05/22/2026

Indication

Treatment of chronic HDV infection in adults without cirrhosis or with compensated cirrhosis

Primary efficacy result

Combined response 48% with HEPCLUDEX vs 2% with delayed treatment at Week 48

Recommended dose

8.5 mg once daily subcutaneous injection

Boxed warning

Posttreatment severe acute exacerbation of hepatitis D and B

Clinical Perspective

Hepatologists, gastroenterologists, infectious disease clinicians, and other prescribers managing adults with chronic HDV infection without cirrhosis or with compensated cirrhosis should be aware that HEPCLUDEX is now an FDA-approved treatment option for this population ^[1]^[2]. The accelerated approval is based on reductions in HDV RNA and ALT normalization observed in Trial MYR301, supporting use where these surrogate endpoints are the treatment goal; continued approval may depend on confirmatory data ^[4]^[1]. What is the optimal treatment duration and the long-term impact on clinical liver outcomes after stopping HEPCLUDEX?

Dr. Sanjay Iyer, MBBS, MD (General Medicine), DM (Gastroenterology) · Gastroenterology

The U.S. Food and Drug Administration approved Hepcludex (bulevirtide-gmod) injection on May 22, 2026, for the treatment of chronic hepatitis delta virus (HDV) infection in adults without cirrhosis or with compensated cirrhosis ^[2]^[1]. Approval was granted under the Accelerated Approval pathway based on Trial MYR301, which showed a combined response of 48% in the Hepcludex group versus 2% in a delayed treatment group at Week 48 ^[2]^[4]. Clinicians should consult current prescribing information for complete dosing guidance.

Clinical Context

HEPCLUDEX (bulevirtide-gmod) is a sodium taurocholate co-transporting polypeptide (NTCP)-directed HDV attachment inhibitor and is the first FDA-approved treatment for chronic HDV infection in the U.S. ^[1]^[2]. The drug is manufactured and marketed by Gilead Sciences, Inc., and its approval addresses a condition for which no FDA-approved therapies previously existed ^[2]^[1]. The accelerated approval was based on virologic and biochemical surrogate endpoints (decrease in HDV RNA and ALT normalization) rather than established clinical outcome benefit; continued approval may be contingent on confirmatory trial(s) ^[1]^[4]. The approved adult population is those without cirrhosis or with compensated cirrhosis ^[1]^[2].

Key Findings

Trial MYR301 showed HEPCLUDEX achieved a combined response of 48% versus 2% with delayed treatment at Week 48; combined response was defined as undetectable HDV RNA (LLOQ 50 IU/mL with target not detected) or ≥ 2 log10 IU/mL decline from baseline and ALT normalization ^[4]^[2].
At Week 48 in MYR301, the virologic response (undetectable HDV RNA or ≥ 2 log10 IU/mL decline) was 76% with HEPCLUDEX versus 4% with delayed treatment ^[4].
The rate of undetectable HDV RNA at Week 48 was 20% in the HEPCLUDEX group versus 0% in the delayed treatment group; in the HEPCLUDEX group undetectable HDV RNA increased to 36% at Week 96 and 50% at Week 144 ^[4]^[2].

Safety & Tolerability

WARNING: Posttreatment severe acute exacerbation of hepatitis D and B may occur after HEPCLUDEX is discontinued; monitor hepatic function, including HBV DNA and HDV RNA, for at least six months after discontinuation ^[1].
Hypersensitivity reactions including anaphylaxis have been reported with HEPCLUDEX ^[1].
Injection site reactions were observed (grouped terms included abscess, erythema, reaction, pruritus, swelling, hematoma, rash, dermatitis, pain) ^[1].
Headache was reported as an adverse reaction ^[1].
Abdominal pain was reported as an adverse reaction ^[1].
Fatigue was reported as an adverse reaction ^[1].
Pruritus (itching) was reported as an adverse reaction and Grade 1 or 2 pruritus occurred in 14% of recipients in MYR301 ^[1].
Eosinophil count increase was reported in MYR301 in 33% of participants (all Grade 1) receiving HEPCLUDEX ^[1].
Total serum bile salts were elevated in all participants who received HEPCLUDEX in MYR301; bile salt elevations resolved upon discontinuation ^[1].

Study Design

The efficacy basis for approval was Trial MYR301 (NCT03852719), a multi-center, randomized, open-label, parallel-arm Phase 3 trial in adults with chronic HDV infection without cirrhosis or with compensated cirrhosis ^[4]. Participants were randomized to immediate HEPCLUDEX 8.5 mg once daily subcutaneous injection for 144 weeks (N=50 in the Immediate Treatment group as reported) or to delayed treatment with an observational period of 48 weeks then HEPCLUDEX 8.5 mg once daily for 96 weeks (Delayed Treatment group N=51 as reported); randomization was stratified by presence or absence of compensated cirrhosis ^[4]^[1]. Clinicians should consult current prescribing information for full dosing guidance. The primary efficacy endpoint was combined response at Week 48, defined as undetectable HDV RNA or ≥ 2 log10 IU/mL decline from baseline and ALT normalization ^[4]. Approval was granted under the Accelerated Approval pathway on May 22, 2026, and a postmarketing requirement was specified to verify and describe clinical benefit ^[2]^[3].

FAQ

Q1 What is HEPCLUDEX (Hepcludex) approved for?

HEPCLUDEX (bulevirtide-gmod) is approved for the treatment of chronic hepatitis delta virus (HDV) infection in adults without cirrhosis or with compensated cirrhosis. The indication received Accelerated Approval based on observed decreases in HDV RNA and normalization of alanine aminotransferase (ALT); an improvement in disease-related clinical outcomes has not been established and continued approval may depend on confirmatory trial(s).

Q2 How does HEPCLUDEX work?

HEPCLUDEX is described in the label as a sodium taurocholate co-transporting polypeptide (NTCP)-directed HDV attachment inhibitor. The label characterizes it as an antiviral that targets HDV/HBV entry via NTCP-mediated mechanisms; mechanistic and clinical pharmacology details are provided in the prescribing information.

Q3 What is the recommended dose of HEPCLUDEX?

The recommended adult dosage is HEPCLUDEX 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. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of HEPCLUDEX?

The most common adverse reactions reported (≥ 10%) were injection site reactions, headache, abdominal pain, fatigue, and pruritus. The labeling includes a boxed warning that severe acute exacerbations of hepatitis D and hepatitis B may occur after discontinuation, and hypersensitivity reactions including anaphylaxis have been reported.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves bulevirtide for chronic HDV: 48% combined response at Week 48

Direct Clinical Takeaway & Evidence Summary

FDA Approves bulevirtide for chronic HDV: 48% combined response at Week 48

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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