FDA Approves Hepcludex (bulevirtide) for Chronic Hepatitis Delta Virus Infection

Hepcludex is a sodium taurocholate co-transporting polypeptide (NTCP)-directed HDV attachment inhibitor.

Hepcludex is indicated for the treatment of chronic hepatitis delta virus (HDV) 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.

The recommended dosage in adults 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. Manage underlying HBV infection as clinically appropriate. If a dose is missed, take it as soon as possible; if almost time for next dose, skip the missed dose. Reconstitute lyophilized powder with 1 mL Sterile Water for Injection and administer immediately. Inject into upper thigh, lower abdomen, or back of upper arm (if given by caregiver).

Efficacy was evaluated in Trial MYR301 (NCT03852719), a Phase 3 open-label trial in 100 participants with chronic HDV infection without cirrhosis or with compensated cirrhosis. Participants received Hepcludex 8.5 mg once daily (protocol specified 10 mg; dose recovery showed 8.5 mg) for 144 weeks or delayed treatment (48-week observation then 96 weeks of Hepcludex). At week 48, combined response (undetectable HDV RNA or ≥2 log10 decline and ALT normalization) was 48% with Hepcludex vs 2% with delayed treatment (p<0.0001). Virologic response was 76% vs 4%, and ALT normalization was 56% vs 12%. Undetectable HDV RNA (<50 IU/mL) was 20% vs 0%.

Not reported in label.

Hepcludex is a first-in-class HDV attachment inhibitor for chronic HDV infection. It is approved under accelerated approval; clinical benefit has not been established. It should be used in patients without cirrhosis or with compensated cirrhosis. Management of underlying HBV infection is recommended.