Brelovitug Meets Primary Endpoint in Phase 3 AZURE-1 Hepatitis Delta Trial

Brelovitug met the primary endpoint in the phase 3 AZURE-1 study of patients with chronic hepatitis delta virus (HDV) infection, Mirum Pharmaceuticals announced on September 28, 2026.¹

At week 24, the combined virologic response and alanine aminotransferase (ALT) normalization endpoint was achieved by 56% of patients receiving 300 mg weekly and 45% receiving 900 mg every 4 weeks, compared with 0% in the delayed treatment group (P < .0001 for both comparisons).¹

Brelovitug is an investigational monoclonal antibody targeting hepatitis B surface antigen (HBsAg). AZURE-1 is one of 2 pivotal phase 3 studies intended to support a US regulatory submission for chronic HDV infection.¹

Related: Inside the AZURE Program of Brelovitug for Hepatitis D, With Tatyana Kushner, MD

"The goal of treating chronic HDV is to prevent progression to cirrhosis, liver cancer and liver failure, and that requires controlling both the virus and liver inflammation," Norah Terrault, MD, MPH, professor of medicine and chief of the Division of GI and Liver at the Keck School of Medicine of the University of Southern California and an AZURE-1 investigator, said in a statement.¹

"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," Terrault said.

AZURE-1 Phase 3 Design and Patient Population

The phase 3 portion of AZURE-1 enrolled 153 treatment naive patients randomized in a 2:2:1 ratio to receive brelovitug 300 mg by subcutaneous injection once weekly (n = 59), brelovitug 900 mg by subcutaneous injection every 4 weeks (n = 65), or delayed treatment beginning at week 24 (n = 29).¹

The primary endpoint was the proportion of patients achieving both virologic response and ALT normalization at week 24. Virologic response was defined as a ≥2 log10 reduction in HDV RNA from baseline or undetectable HDV RNA (target not detected [TND]).¹

Brelovitug Virologic Response and ALT Normalization at Week 24

Mirum also reported the following individual efficacy outcomes at week 24:¹

• Virologic response: 86% with brelovitug 300 mg weekly and 85% with 900 mg every 4 weeks, compared with 0% with delayed treatment.
• HDV RNA below the lower limit of quantification (LLOQ; <10 IU/mL): 25% and 26%, respectively, compared with 0%.
• HDV RNA TND: 17% in each brelovitug group, compared with 0%.
• ALT normalization: 63% with 300 mg weekly and 54% with 900 mg every 4 weeks, compared with 0%.

Individual virologic response and ALT normalization rates were greater than the composite endpoint rates because the primary endpoint required both outcomes in the same patient.

Brelovitug Safety: Adverse Events Through Week 24

At least 1 adverse event (AE) occurred in 45.8% of patients receiving brelovitug 300 mg weekly and 61.5% receiving 900 mg every 4 weeks, compared with 27.6% in the delayed treatment group. Treatment related AEs occurred in 23.7%, 33.8%, and 0% of patients, respectively.¹

No grade ≥3 AEs, serious AEs, or AEs leading to treatment discontinuation were reported in either brelovitug group through week 24. In the delayed treatment group, 1 patient (3.4%) experienced a grade 4 acute myocardial infarction, which was classified as a serious AE.¹

Injection site reactions occurred in 10.2% of patients receiving brelovitug 300 mg weekly and 18.5% receiving 900 mg every 4 weeks. Flulike symptoms occurred in 5.1% and 10.8%, respectively. Neither event type was reported in the delayed treatment group.¹

AZURE-1 Phase 2b Data Show Responses Through Week 48

In April 2026, Mirum reported that the phase 2b portion of AZURE-1 met its primary endpoint at week 24 in both brelovitug dose groups.³ The company has now reported week 48 efficacy findings from this earlier cohort, which included the first 53 patients enrolled in the study, with 20 patients per dose group included in the week 24 and week 48 efficacy analyses.¹

The combined primary endpoint increased from 45% at week 24 to 55% at week 48 among patients receiving brelovitug 300 mg weekly. In the 900 mg every 4 weeks group, the rate increased from 35% to 55%.¹

Additional findings included:

• Virologic response: 100% at week 24 and 95% at week 48 with 300 mg weekly; 75% and 95%, respectively, with 900 mg every 4 weeks.
• HDV RNA below the LLOQ: 45% at week 24 and 80% at week 48 with 300 mg weekly; 10% and 40%, respectively, with 900 mg every 4 weeks.
• HDV RNA TND: 35% at week 24 and 40% at week 48 with 300 mg weekly; 5% and 25%, respectively, with 900 mg every 4 weeks.
• ALT normalization: 45% at week 24 and 55% at week 48 with 300 mg weekly; 40% and 55%, respectively, with 900 mg every 4 weeks.
• Mirum reported no new safety signals through week 48.¹

"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," Chari A. Cohen, DrPH, MPH, president of the Hepatitis B Foundation, said in a statement. "Results like these bring hope to a community that has had few options until recently."¹

Next Steps for Brelovitug Development

Mirum expects topline results from the phase 3 AZURE-4 study in the fourth quarter of 2026 and plans to submit a biologics license application (BLA) to the US Food and Drug Administration (FDA) in the first half of 2027. The company has projected a potential US commercial launch in the fourth quarter of 2027.¹

In May 2026, the FDA granted accelerated approval to bulevirtide (Hepcludex), the first treatment approved for chronic HDV in the US.²

Brelovitug has received FDA Breakthrough Therapy designation and PRIME and orphan designations from the European Medicines Agency.¹

"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 and clinically significant portal hypertension," Nancy Shulman, MD, executive vice president of clinical development at Mirum, said in a statement.¹

The full phase 3 AZURE-1 results are expected to be presented at an upcoming medical congress.¹

References

1. Mirum Pharmaceuticals. Mirum Pharmaceuticals announces primary endpoint met in phase 3 AZURE-1 study of brelovitug in chronic hepatitis delta virus. 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

2. US Food and Drug Administration. FDA approves first treatment for chronic hepatitis delta virus (HDV) infection. May 22, 2026. Accessed September 28, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-chronic-hepatitis-delta-virus-hdv-infection

3. Mirum Pharmaceuticals. Mirum Pharmaceuticals announces primary endpoint met in phase 2b portion of the AZURE-1 study of brelovitug in chronic hepatitis delta virus. April 27, 2026. Accessed September 28, 2026. https://ir.mirumpharma.com/news/news-details/2026/Mirum-Pharmaceuticals-Announces-Primary-Endpoint-Met-in-Phase-2b-Portion-of-the-AZURE-1-Study-of-Brelovitug-in-Chronic-Hepatitis-Delta-Virus/default.aspx