Brelovitug (Mirum Pharmaceuticals) met the primary end point in the phase 3 portion of the phase 2b/3 AZURE-1 study in treatment-naive patients with chronic hepatitis delta virus (HDV), according to a company statement.1 At week 24, 56% of patients receiving 300 mg weekly and 45% receiving 900 mg every four weeks achieved combined virologic response and alanine aminotransferase (ALT) normalization, compared with 0% in the delayed treatment arm (P < .0001 for both comparisons).1 Mirum plans a biologics license application submission in the first half of 2027.1
Brelovitug is a fully human immunoglobulin G1 monoclonal antibody targeting hepatitis B surface antigen (HBsAg). The agent holds FDA breakthrough therapy designation for chronic HDV, along with PRIME and orphan designations from the European Medicines Agency. Mirum said no treatments are currently approved by the FDA for hepatitis D.1
Brelovitug Efficacy in Phase 3 AZURE-1 Study
AZURE-1 enrolled approximately 200 treatment-naive patients, randomized 2:2:1 to brelovitug 300 mg weekly by subcutaneous injection, brelovitug 900 mg every four weeks, or delayed treatment. Patients in the delayed arm began 300 mg weekly after a 24-week control period. The study included patients with advanced disease, cirrhosis, and clinically significant portal hypertension.1
The primary end point was the proportion of patients with combined virologic response, defined as a 2 log10 or greater reduction in HDV RNA from baseline or undetectable HDV RNA, plus ALT normalization at week 24.1 In the phase 3 analysis, 56% of patients in the 300-mg weekly arm (n = 59) and 45% in the 900-mg arm (n = 65) met the primary end point, compared with 0% in the delayed arm (n = 29). Virologic response occurred in 86% and 85% of patients, respectively, and ALT normalized in 63% and 54%.
HDV RNA fell below the lower limit of quantification (less than 10 IU/mL) in 25% and 26% of patients, and was undetectable in 17% of patients in both arms.
Frequently Asked Questions
What is Brelovitug being studied for?
Brelovitug is an investigational monoclonal antibody studied for chronic HDV infection. Mirum plans a biologics license application submission in the first half of 2027.
How does Brelovitug work?
Brelovitug is a fully human IgG1 monoclonal antibody targeting HBsAg. It neutralizes and removes hepatitis B and hepatitis D virions and depletes HBsAg-containing subviral particles.
What did the AZURE-1 study show?
At week 24, 56% of patients on 300 mg weekly and 45% on 900 mg every four weeks met the combined virologic response and ALT normalization end point, compared with 0% on delayed treatment (P < .0001).
Brelovitug Safety Profile and 48-week Phase 2b data
Through week 24, any adverse event occurred in 45.8% of patients in the 300-mg weekly arm (n = 27) and 61.5% in the 900-mg arm (n = 40), compared with 27.6% in the delayed arm (n = 8). Treatment-related adverse events occurred in 23.7% and 33.8% of patients in the brelovitug arms, respectively, and in none of the delayed arm. No grade 3 or higher adverse events, serious adverse events, or discontinuations due to adverse events occurred in either brelovitug arm.1
Injection site reactions (10.2% and 18.5%) and flu-like symptoms (5.1% and 10.8%) were the most common adverse events in the 300-mg and 900-mg arms. One patient in the delayed arm had a grade 4 acute myocardial infarction, classified as a serious adverse event.
In the phase 2b cohort (n = 20 per arm), the primary end point rate rose from 45% at week 24 to 55% at week 48 with 300 mg weekly, and from 35% to 55% with 900 mg every four weeks.1 Mirum reported no new safety signals through 48 weeks.
"Seeing virologic response alongside ALT normalization is encouraging in a long-term therapy," said Norah Terrault, MD, MPH, chief of the GI and Liver Division at the Keck School of Medicine of USC and an AZURE-1 investigator, in a news release.1
Topline results from the second pivotal phase 3 study, AZURE-4, are expected in the fourth quarter of 2026.1 Mirum projects a potential US launch in the fourth quarter of 2027 and hosted an investor call on September 28 to review the data.2
References
Mirum Pharmaceuticals. Mirum Pharmaceuticals announces primary endpoint met in Phase 3 AZURE-1 study of brelovitug in chronic hepatitis delta virus. News release. Published September 28, 2026. Accessed September 28, 2026. https://ir.mirumpharma.com/news/news-details/2026/Mirum-Pharmaceuticals-Announces-Primary-Endpoint-Met-in-Phase-3-AZURE-1-Study-of-Brelovitug-in-Chronic-Hepatitis-Delta-Virus/default.aspx
Mirum Pharmaceuticals. Mirum Pharmaceuticals to host investor call to share topline results from the Phase 3 AZURE-1 study of brelovitug in chronic hepatitis delta on September 28, 2026. News release. Business Wire. Published September 27, 2026. Accessed September 28, 2026. https://www.businesswire.com/news/home/20260927892676/en/Mirum-Pharmaceuticals-to-Host-Investor-Call-to-Share-Topline-Results-from-the-Phase-3-AZURE-1-Study-of-Brelovitug-in-Chronic-Hepatitis-Delta-on-September-28-2026
