Mirum Pharmaceuticals reports positive Phase 3 AZURE-1 results for brelovitug in chronic HDV, with virologic response and ALT normalization at Week 24.
Written By: Neha Vishwakarma, PharmD
Reviewed By: Pharmacally Editorial Team
Mirum Pharmaceuticals has announced that the Phase 3 portion of AZURE-1, a pivotal Phase 2b/3 trial evaluating brelovitug in chronic hepatitis delta virus (HDV) infection, met its primary endpoint at Week 24. The company also reported 48-week data from the Phase 2b portion of the study, showing deeper viral suppression and higher rates of alanine aminotransferase (ALT) normalization with longer treatment.
Brelovitug is an investigational, fully human IgG1 monoclonal antibody that targets hepatitis B surface antigen (HBsAg), a key surface protein present on both HDV and HBV particles. By binding HBsAg, brelovitug is designed to neutralize circulating HDV and HBV virions and facilitate their removal from the bloodstream, while also depleting HBsAg-containing subviral particles. This mechanism is intended to reduce viral levels and potentially decrease the ongoing liver inflammation associated with chronic HDV infection.
Phase 3 Results in Chronic HDV
The Phase 3 portion of AZURE-1 enrolled 153 treatment-naive patients who were randomized 2:2:1 to brelovitug 300 mg subcutaneously once weekly (n=59), brelovitug 900 mg subcutaneously every four weeks (n=65), or a 24-week delayed-treatment arm (n=29). Patients in the delayed-treatment group began brelovitug 300 mg weekly after the delay period.
The primary endpoint was the proportion of patients achieving both a virologic response and ALT normalization at Week 24. Virologic response was defined as a reduction in HDV RNA of at least 2 log10 from baseline or undetectable HDV RNA (target not detected, TND).
The primary endpoint was achieved by 56% of patients receiving 300 mg weekly and 45% receiving 900 mg every four weeks, compared with 0% in the delayed-treatment group. Both comparisons were statistically significant (p<0.0001; stratum-adjusted Miettinen-Nurminen test).
Results for the individual components at Week 24 were as follows:
- Virologic response: 86% with 300 mg weekly and 85% with 900 mg every four weeks, versus 0% with delayed treatment.
- HDV RNA below the lower limit of quantification (<10 IU/mL): 25% and 26%, respectively, versus 0%.
- HDV RNA TND: 17% in each brelovitug group, versus 0%.
- ALT normalization: 63% with the weekly dose and 54% with the four-weekly dose, versus 0%.
The individual response rates were higher than the composite endpoint because the primary endpoint required both virologic response and ALT normalization in the same patient.
Safety Profile Through Week 24
At least one adverse event occurred in 45.8% of patients receiving the weekly dose and 61.5% receiving the four-weekly dose, compared with 27.6% in the delayed-treatment group. Treatment-related adverse events were reported in 23.7% and 33.8% of the brelovitug groups, respectively, and in none of the delayed-treatment patients.
No grade 3 or higher adverse events, serious adverse events, or events leading to treatment discontinuation were reported in either brelovitug arm through Week 24. One patient in the delayed-treatment group experienced a grade 4 acute myocardial infarction, which was classified as a serious adverse event.
Injection-site reactions occurred in 10.2% of patients receiving the weekly dose and 18.5% receiving the four-weekly dose. Flu-like symptoms occurred in 5.1% and 10.8%, respectively. Neither event was reported in the delayed-treatment group.
48-Week Data from the Phase 2b Portion
The Phase 2b portion of AZURE-1 included the first 53 patients enrolled in the study. The Week 24 and Week 48 efficacy analyses included 20 evaluable patients in each dose group. Mirum had previously reported that this cohort met its primary endpoint at Week 24 in April 2026.
Among patients receiving 300 mg weekly, the combined endpoint increased from 45% at Week 24 to 55% at Week 48. In the 900 mg every-four-weeks group, it increased from 35% to 55%.
Further findings at Week 24 and Week 48 included:
- Virologic response: 100% and 95% with the weekly dose, and 75% and 95% with the four-weekly dose.
- HDV RNA below the lower limit of quantification: 45% and 80% with the weekly dose, and 10% and 40% with the four-weekly dose.
- HDV RNA TND: 35% and 40% with the weekly dose, and 5% and 25% with the four-weekly dose.
- ALT normalization: 45% and 55% with the weekly dose, and 40% and 55% with the four-weekly dose.
Mirum reported no new safety signals through Week 48.
Expert Perspective
Norah Terrault, M.D., M.P.H., an AZURE-1 investigator and chief of the Division of GI and Liver at the Keck School of Medicine of USC, said effective chronic HDV treatment requires control of both viral replication and liver inflammation. She noted that achieving ALT normalization alongside virologic response is encouraging for long-term treatment.
Nancy Shulman, M.D., Mirum’s executive vice president of clinical development, said the results support brelovitug as a well-tolerated, convenient single-agent therapy, with responses observed across patients with significant liver inflammation, cirrhosis and clinically significant portal hypertension. Chari A. Cohen, Dr.P.H., M.P.H., president of the Hepatitis B Foundation, emphasized the need for durable and tolerable treatment options for chronic HDV.
Development and Regulatory Plans
AZURE-1 is one of two pivotal Phase 3 studies supporting Mirum’s U.S. registration strategy for brelovitug. Topline results from AZURE-4 are expected in the fourth quarter of 2026, followed by a planned BLA submission in the first half of 2027 and a potential U.S. launch in the fourth quarter of 2027. Brelovitug has received FDA Breakthrough Therapy designation and EMA PRIME and orphan designations.
The U.S. HDV treatment landscape changed in May 2026 with the FDA’s accelerated approval of Hepcludex (bulevirtide-gmod), the first FDA-approved treatment for chronic HDV in adults without cirrhosis or with compensated cirrhosis. AZURE-1 is evaluating brelovitug in approximately 200 treatment-naive patients overall, with open-label follow-up of up to 96 weeks.
Reference
Mirum Pharmaceuticals Announces Primary Endpoint Met in Phase 3 AZURE-1 Study of Brelovitug in Chronic Hepatitis Delta Virus, Mirum Pharmaceuticals, 28 September 2026
A Trial Evaluating BJT-778 vs Delayed Treatment for the Treatment of Chronic Hepatitis Delta Infection, ClinicalTrials.gov ID NCT06907290
About the Writer
Neha Vishwakarma (Linkedin) is a Pharm.D professional with experience in clinical pharmacy, pharmacovigilance, and clinical research. She has hands-on experience in ADR assessment, ICSR processing, medication safety, and clinical data evaluation. Her research background in surgical site infections and antibiotic use supports her focus on evidence-based healthcare writing.