FDA grants accelerated approval to bulevirtide, the first US therapy for chronic hepatitis delta

The clearance rests on a 150-patient trial showing a combined virologic-and-biochemical surrogate response; whether the drug improves clinical outcomes is still unproven.

The FDA has granted accelerated approval to bulevirtide (Hepcludex, bulevirtide-gmod), the first treatment cleared in the United States for chronic hepatitis delta virus (HDV) infection, the most aggressive form of viral hepatitis. The drug, from Gilead Sciences, is indicated for adults without cirrhosis or with compensated cirrhosis and is given as an 8.5 mg once-daily subcutaneous injection.

Approval was based on MYR301 (NCT03852719), an open-label Phase 3 trial that randomized 150 patients to bulevirtide 2 mg daily, bulevirtide 10 mg daily, or delayed treatment as the control arm.

What the trial showed

The primary endpoint was combined response at Week 48, defined as undetectable HDV RNA or a decrease of at least 2 log10 IU/mL, plus normalization of ALT. In the 10 mg arm, 48.0% of patients met that endpoint, versus 2.0% on delayed treatment, a difference of 46.0 percentage points (96% CI, 30.5 to 61.4; p<0.0001, Fisher exact). The 2 mg arm reached 44.9%.

Combined virologic and biochemical response is a surrogate; whether bulevirtide changes clinical outcomes such as liver failure or death has not been established.

On secondary endpoints at Week 48, undetectable HDV RNA was reached by 20.0% of the 10 mg arm versus none of the controls, and ALT normalized in 56.0% versus 11.8%.

Because the approval is accelerated and rests on surrogate measures, Gilead must verify clinical benefit in a confirmatory trial. The label carries a boxed warning for post-treatment severe acute exacerbation of hepatitis D and B, with monitoring advised for at least six months after the drug is stopped. HDV, which infects only people already carrying hepatitis B, had no FDA-approved therapy before this clearance.

Trials Today

Phase 3 VECTRA-01 (AZD2265 / 225Ac-PSMA-I&T, mCRPC) — Recruiting; alpha-emitter PSMA radioligand vs SOC after prior beta-emitter, taxane and ARPI; ~670 patients; dual primary rPFS and OS.

Phase 3 PRECISE-HD (pridopidine, Huntington's disease) — Newly registered; 400 patients not on antidopaminergics; primary is 52-week change in composite cUHDRS.

Phase 3 QUILT-2.023 (nogapendekin alfa inbakicept, 1L NSCLC) — Terminated; sponsor registry note states no active subjects, no efficacy results posted (enrolled 102).

Phase 3 Atezolizumab + standard HER2 therapy, 1L HER2+ mBC (NRG/NCI) — Terminated for poor accrual (190 enrolled); posted PFS 52.3% vs 40.5% is a numerical, underpowered signal only (CIs overlap, no HR).

Phase 2/3 Peri-operative nivolumab + ipilimumab, esophageal/GEJ adenocarcinoma (NCI) — Suspended after enrolling 278; registry summary gives no reason, so cause is unconfirmed. Watch item.

At the Agencies

Baxdrostat (Baxfendy), AstraZeneca — FDA approval May 18, 2026; first-in-class aldosterone synthase inhibitor for uncontrolled/resistant hypertension; BaxHTN placebo-adjusted SBP -9.8 mmHg.

Bulevirtide (Hepcludex), Gilead — FDA accelerated approval May 22, 2026; first US therapy for chronic hepatitis delta; surrogate week-48 combined response 48% vs 2%, confirmatory data required.

Pivekimab sunirine (Decnupaz), AbbVie — FDA approval May 27, 2026; first CD123-directed ADC for ultra-rare BPDCN; single-arm CADENZA CR/CRc 69.7% in treatment-naive (n=33).

Nerandomilast (Jascayd), Boehringer Ingelheim — EMA CHMP — Positive CHMP opinion (18-21 May 2026) for IPF and PPF; oral PDE4B inhibitor; FIBRONEER-IPF met primary FVC endpoint, key secondary not met. EC decision pending.