Development

Mirum's brelovitug aces Phase III in chronic hepatitis delta virus with 56% response rate

Mirum's brelovitug aces Phase III in chronic hepatitis delta virus with 56% response rate

Mirum Pharmaceuticals (Nasdaq: MIRM) reported that the Phase III portion of the AZURE-1 study of brelovitug, an anti-hepatitis B surface antigen (HBsAg) monoclonal antibody, met its primary composite endpoint of virologic response and alanine aminotransferase (ALT) normalization at Week 24 in treatment-naive patients with chronic hepatitis delta virus (HDV).

The AZURE-1 Phase IIb/III study randomized 153 treatment-naive patients in its Phase III portion to brelovitug 300 mg weekly, 900 mg every four weeks, or delayed treatment. At Week 24, the composite endpoint of virologic response and ALT normalization was met by 56% and 45% of patients in the two active arms, respectively, versus 0% with delayed treatment (p<0.0001 for both). Virologic response rates were 86% and 85%.

Responses continued to deepen through Week 48 in the Phase IIb portion. In the Phase III cohort, no Grade ≥3 adverse events, serious adverse events, or discontinuations were reported through Week 24; injection-site reactions and flu-like symptoms were the main tolerability findings.

Brelovitug is a fully human IgG1 monoclonal antibody that targets HBsAg on both HDV and hepatitis B virus (HBV) virions, designed to neutralize HBsAg-containing subviral particles and enhance antigen-specific T cell activation — a mechanism distinct from Gilead Sciences' Hepcludex (bulevirtide-gmod), which blocks viral entry via the host sodium taurocholate co-transporting polypeptide (NTCP) receptor.

Gilead received FDA accelerated approval for bulevirtide in chronic HDV in May 2026, based on a 48% combined endpoint response rate, and the drug had previously received full EU marketing authorization in 2024. Vir Biotechnology is running a Phase III program evaluating the combination of tobevibart and elebsiran in HDV. Cross-trial comparisons are constrained by differences in patient populations, endpoints, and follow-up duration.

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Brelovitug holds FDA Breakthrough Therapy designation, Orphan Drug designation, and Priority Medicines (PRIME) status from the European Medicines Agency (EMA) for chronic HDV.

Mirum acquired brelovitug through its purchase of Bluejay Therapeutics, completed in January 2026 for USD 250 million in cash and USD 370 million in Mirum common stock, plus potential tiered sales-based milestone payments of up to USD 200 million in cash.

Mirum said it plans to submit a Biologics License Application (BLA) to the FDA in H1 2027, targeting a potential US commercial launch in Q4 2027. Topline results from the Phase III AZURE-4 study, the second pivotal trial intended to support the registration package, are expected in Q4 2026.


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