Mirum's Brelovitug Hits Primary Endpoint in Phase 3 AZURE-1 Study of Chronic Hepatitis Delta
核心洞察
Mirum Pharmaceuticals reported that brelovitug met the primary endpoint in the Phase 3 portion of the AZURE-1 study in chronic hepatitis delta virus (搜索) infection.
At Week 24, 56% of patients on brelovitug 300 mg weekly and 45% on 900 mg every four weeks achieved combined virologic response and ALT normalization.
48-week Phase 2b data showed deepening viral suppression, more patients reaching HDV RNA below the limit of quantification, and higher rates of ALT normalization.
Mirum Pharmaceuticals announced that the primary endpoint was met in the Phase 3 portion of the AZURE-1 study of brelovitug, an investigational fully human monoclonal antibody that binds hepatitis B surface antigen (HBsAg), in patients with chronic hepatitis delta virus (搜索) (HDV) infection. The company also reported 48-week data from the Phase 2b portion of the same study showing deepening viral suppression and increased rates of alanine aminotransferase (ALT) normalization with longer treatment.
AZURE-1 is one of two pivotal Phase 3 studies intended to form the basis of Mirum's U.S. registration package for brelovitug.
Phase 3 Efficacy at Week 24
The Phase 3 portion of AZURE-1 enrolled 153 treatment-naive patients randomized in a 2:2:1 ratio to brelovitug 300 mg self-administered once weekly (QW) by subcutaneous (SC) injection, brelovitug 900 mg administered once every four weeks (Q4W) by SC injection, or delayed treatment starting at Week 24. The global study enrolled a broad patient population that included patients with advanced disease.
At Week 24, 56% of patients in the 300 mg QW arm and 45% in the 900 mg Q4W arm achieved the combined primary endpoint of virologic response, defined as a 2 log10 or greater reduction in HDV RNA from baseline or undetectable HDV RNA, together with ALT normalization.
"These results demonstrate the potential of brelovitug as a well-tolerated, convenient, single agent to deliver both deep viral suppression and ALT normalization, with responses that continue to deepen through 48 weeks of treatment. Notably, these results were achieved in a broad patient population, including those with significant liver inflammation, cirrhosis (搜索) and clinically significant portal hypertension," said Nancy Shulman, M.D., Executive Vice President of Clinical Development at Mirum.
Treatment with brelovitug was well tolerated across dose groups, with a safety profile consistent with previously reported AZURE-1 data and no new safety signals.
Deepening Responses Through 48 Weeks
The Phase 2b portion of AZURE-1 included the first 53 patients enrolled in the study. After the previously reported Week 24 primary analysis, patients continued treatment in the open-label extension. Between Week 24 and Week 48, viral suppression deepened and rates of ALT normalization increased, with a greater proportion of patients achieving HDV RNA below the lower limit of quantification (LLOQ, less than 10 IU/mL) and target not detected (TND). Safety through Week 48 was consistent with previously reported results, with no new safety signals observed.
"The goal of treating chronic HDV is to prevent progression to cirrhosis (搜索), liver cancer (搜索) and liver failure, and that requires controlling both the virus and liver inflammation," said Norah Terrault, M.D., MPH, Professor of Medicine and Chief of the Division of GI and Liver at the Keck School of Medicine of USC, and an AZURE-1 investigator. "ALT is a marker of liver injury, so seeing virologic response alongside ALT normalization is encouraging in a long-term therapy. For patients facing the most aggressive form of viral hepatitis, these are important results."
Unmet Need in Hepatitis Delta
HDV occurs in some people infected with hepatitis B virus (搜索) and is described by Mirum as the most severe form of viral hepatitis because of the potential for rapid progression to liver cirrhosis (搜索), liver cancer (搜索) and liver-related death. The infection affects approximately 230,000 people in the United States and Europe, and it is estimated that more than 50% of individuals with HDV will die of liver-related causes within 10 years of diagnosis. There are currently no approved treatments for HDV in the United States and in most countries worldwide.
"Chronic hepatitis delta is a lifelong disease, and people living with it need treatment options that are effective, safe and tolerable enough to stay on over time. That's especially true for patients with more advanced disease, who often have the fewest choices," said Chari A. Cohen, DrPH, MPH, President of the Hepatitis B Foundation. "Results like these bring hope to a community that has had few options until recently."
Mechanism and Regulatory Status
Brelovitug is an investigational, highly potent, pan-genotypic, fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting the surface antigen (anti-HBsAg) on both HDV and hepatitis B virus (搜索) (HBV). It is designed to neutralize and remove hepatitis B and hepatitis D virions and to deplete HBsAg-containing subviral particles. The antibody holds FDA Breakthrough Therapy designation for chronic HDV and PRIME and Orphan designations from the European Medicines Agency. Mirum owns worldwide rights to brelovitug.
In April 2026, Mirum reported that in the Phase 2b portion of AZURE-1, brelovitug demonstrated strong antiviral activity in HDV and achieved the primary combined endpoint of virologic response and ALT normalization at Week 24 in both dose arms compared with the delayed treatment arm, with favorable safety and tolerability.
Next Steps in the AZURE Program
The AZURE program is a global, registrational Phase 3 development program evaluating brelovitug in chronic HDV. It includes multiple open-label studies designed to assess the primary endpoint of combined virologic response and ALT normalization, and the studies together are intended to support regulatory filings in the United States and Europe. AZURE-1 has enrolled approximately 200 treatment-naive patients, with open-label extension periods of up to 96 weeks.
Full results from the Phase 3 AZURE-1 study will be presented at an upcoming medical congress. Topline results from the Phase 3 AZURE-4 study, the second pivotal study supporting the U.S. registration package, are expected in Q4 2026. Mirum expects to submit a Biologics License Application to the U.S. Food and Drug Administration (搜索) in the first half of 2027, with potential U.S. commercial launch in Q4 2027.