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

For clinicians managing hepatitis D virus (HDV) infection, the stakes are uniquely high. Unlike many other chronic viral hepatitides, HDV is widely recognized as the most aggressive form of viral hepatitis, often leading to rapid disease progression and severe long-term complications.

In an interview with HCPLive, Tatyana Kushner, MD, an associate professor of medicine in the division of gastroenterology and hepatology at Weill Cornell Medicine, explained how the inflammatory nature of the disease drives this aggressive clinical course. Patients frequently experience significant liver inflammation and elevated viral activity, accelerating progression to advanced liver disease.

Check out part 1 of the interview with Kushner here.

“Delta hepatitis is the most rapidly progressive form of hepatitis,” Kushner explained, noting that clinicians commonly see complications develop earlier than expected compared with other viral infections.

The consequences can be striking in clinical practice. Kushner noted that she regularly encounters patients in their 30s and 40s who have already developed cirrhosis, an outcome far less common among individuals with isolated hepatitis B infection. Because HDV relies on hepatitis B virus for replication, coinfection can significantly worsen liver outcomes.

Given this aggressive trajectory, treatment goals focus on achieving both virologic and biochemical control. Ideally, she says therapies would reduce HDV RNA to undetectable levels while normalizing liver enzymes such as ALT, which reflect ongoing hepatic inflammation. Achieving these surrogate markers could ultimately translate into reduced risk of cirrhosis, hepatocellular carcinoma, and liver transplantation.

Emerging therapies are now being evaluated with these goals in mind. Kushner highlights brelovitug, an investigational monoclonal antibody being developed by Mirum Pharmaceuticals and currently studied in the AZURE program, as one of the most promising.

The global, registrational phase 3 clinical development program includes multiple open-label studies designed to assess the primary endpoint of combined virologic and biochemical response. Together, the studies are intended to support regulatory filings in the United States and Europe. Topline data from AZURE-1 and AZURE-4 are expected in 2H 2026, with a potential BLA submission and launch in the US in 2027.

The primary endpoint for both studies is the proportion of patients achieving combined virologic response and ALT normalization at week 24, comparing brelovitug with a delayed-treatment control group and consistent with FDA guidance for accelerated approval in HDV.

Patients enrolled in the study will remain on treatment beyond the 24-week primary endpoint, allowing investigators to evaluate longer-term outcomes. Secondary analyses will focus on safety and tolerability, which remain critical considerations given the limitations of historical treatments such as pegylated interferon.

Beyond traditional clinical endpoints, the trial will also examine exploratory measures including patient-reported outcomes and quality of life. Kushner emphasized that these assessments are particularly meaningful in HDV, where patients have historically faced years of uncertainty without effective treatment options.

Looking ahead, Kushner believes the field is approaching an important turning point. While early efforts are focused on establishing therapies that are both effective and tolerable, the long-term goal will be demonstrating improvements in hard clinical outcomes, such as reduced rates of cirrhosis and liver cancer.

“I think we're getting pretty close to having several treatment options that achieve those desired outcomes. Over the years, as patients stay on these treatments longer, we will really want to see hard clinical endpoints, improvement in fibrosis, decreased incidence of cirrhosis and liver cancer in patients who are on these treatments long term,” Kushner said. “I think it will be important to think about not just long term treatment options, but finite treatment options… Before we get there, finding treatments that, even if long term, can have meaningful clinical, beneficial endpoints, it will be a big accomplishment.”

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

References

1. World Health Organization. Hepatitis D. July 25, 2025. Accessed March 13, 2026. https://www.who.int/news-room/fact-sheets/detail/hepatitis-d

2. Mirum Pharmaceuticals. Mirum Pharmaceuticals Completes AZURE-1 Enrollment and AZURE-4 Screening in Phase 3 Program of brelovitug in Chronic Hepatitis Delta Virus. March 5, 2026. Accessed March 13, 2026. https://ir.mirumpharma.com/news/news-details/2026/Mirum-Pharmaceuticals-Provides-AZURE-Clinical-Program-Update-for-brelovitug-in-Chronic-Hepatitis-Delta-Virus/default.aspx