AZURE-1: Brelovitug Meets Key Endpoints in Hepatitis D, With Tatyana Kushner, MD

As interest grows in therapeutic development for hepatitis D virus (HDV), understanding how clinical trial endpoints translate into meaningful patient benefit remains a critical focus for clinicians. Unlike more common liver diseases, HDV trials rely on well-defined surrogate markers that reflect both viral activity and liver health. These endpoints are not only essential for regulatory evaluation but also serve as key indicators of whether emerging therapies may alter the natural history of this aggressive disease.

In the phase 2b portion of the AZURE-1 study, investigational agent brelovitug demonstrated success against the US Food and Drug Administration (FDA)-specified composite primary endpoint, which includes at least a 2-log reduction in HDV RNA alongside normalization of alanine aminotransferase (ALT). In an interview with HCPLive, Tatyana Kushner, MD, emphasized that while this endpoint is considered a surrogate, it is strongly associated with clinically meaningful outcomes.

Check out part 1 of the interview with Kushner here.

“We care about both,” she explained, pointing to the importance of reducing viral replication while simultaneously improving liver inflammation, as reflected by ALT levels.

In the study, brelovitug met the primary endpoint across multiple dosing arms, reinforcing its potential as a therapeutic option in a space where treatment choices remain extremely limited. Beyond the binary endpoint achievement, Kushner highlighted the continuous decline in HDV RNA over time among treated patients, suggesting that longer treatment durations could yield even greater response rates, a question that ongoing and future analyses will aim to address.

For both clinicians and patients, these improvements are more than abstract metrics. Virologic decline offers tangible reassurance that the virus is being suppressed, while normalization of ALT provides evidence of reduced liver inflammation. Kushner noted that patients are often highly attuned to these laboratory values, particularly after years of limited treatment options and persistently abnormal results. The hope is that these biochemical improvements will ultimately translate into downstream clinical benefits, including reduced fibrosis progression and lower risk of liver-related complications.

According to phase 2b findings, brelovitug was generally well tolerated, with the most commonly reported adverse events being injection site reactions, an expected finding for a subcutaneous therapy. Of note, the flu-like symptoms frequently associated with pegylated interferon were largely absent. This distinction could represent a meaningful advantage in real-world practice, where tolerability often limits treatment uptake and persistence.

The study population itself further underscores the significance of these findings. Kushner pointed out that AZURE-1 included patients with a broad range of disease severity, without strict limitations on baseline ALT levels or fibrosis stage. As a result, some participants had advanced liver disease, including compensated cirrhosis, and potentially significant portal hypertension. Despite this higher-risk population, brelovitug demonstrated both efficacy and tolerability, strengthening confidence in its potential applicability across a wide spectrum of patients.

Editors’ Note: Kushner reports relevant disclosures with Gilead, Abbvie, GSK, Ipsen, Mirum, and Madrigal.

References

1. US Centers for Disease Control and Prevention. Hepatitis D Basics. April 24, 2024. Accessed April 29, 2026. https://www.cdc.gov/hepatitis-d/about/index.html

2. Ghany MG, Pan CQ, Lok AS, et al. AASLD ISDA Practice Guideline on treatment of chronic hepatitis B. Hepatology. Published online November 4, 2025. doi:10.1097/HEP.0000000000001549

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 April 29, 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