Tatyana Kushner, MD, is an associate professor of medicine in the division of gastroenterology and hepatology at Weill Cornell Medicine.

Tatyana Kushner, MD

New Hope for Hepatitis D? Brelovitug and the AZURE Program

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.

, 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 

“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.

World Health Organization. Hepatitis D. July 25, 2025. Accessed March 13, 2026. 

https://www.who.int/news-room/fact-sheets/detail/hepatitis-d

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

Videos

With new therapies emerging for hepatitis D, Kushner discusses brelovitug’s potential and what will be learned from the phase 3 AZURE program.

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

Hepatitis D: Burden, Testing Gaps, and Emerging Therapies

Despite growing awareness of hepatitis D virus (HDV) infection, experts say the true burden of the disease remains difficult to define, with limited testing, gaps in provider awareness, and historically restricted access to diagnostics all contributing to persistent uncertainty about epidemiology.

, Tatyana Kushner, MD, an associate professor of medicine in the division of gastroenterology and hepatology at Weill Cornell Medicine, noted that routine testing for HDV was not widely recommended until relatively recently, leaving significant blind spots in prevalence estimates. Much of what clinicians know today is based on patients who were tested, diagnosed, and subsequently documented through diagnostic codes or laboratory confirmation. Patients who were never tested, however, remain invisible in these data.

“Up until relatively recently, there was no recommended routine testing for delta hepatitis, and there was somewhat limited access to appropriate testing,” she said. “On top of that, there is still a lack of knowledge about delta hepatitis, so providers don't know who to test, when to test, and about delta hepatitis in general.”

As a result, Kushner noted that prevalence estimates did not include a large portion of patients because they were not being tested or diagnosed. As this has improved over time and experts get a better understanding of HDV epidemiology, geographic gaps in prevalence have become increasingly evident.

Certain regions of the world, including parts of Eastern Europe, Central Asia, and Africa, have a substantially greater prevalence of HDV. In the United States, many patients diagnosed with the infection originate from these endemic regions. However, clinicians are increasingly identifying cases among US-born individuals, raising new questions about transmission patterns and risk factors that are not yet fully understood.

Kushner emphasizes that expanding education and improving access to testing will be critical to refining prevalence estimates. As awareness grows among clinicians and screening becomes more common, researchers may begin to develop a clearer understanding of HDV’s true national and global burden.

At the same time, the treatment landscape for HDV is beginning to evolve after decades of limited therapeutic options. In the absence of US Food and Drug Administration-approved treatments, current guidance from the American Association for the Study of Liver Diseases recommends off-label use of pegylated interferon for patients with active infection who do not have contraindications. However, this therapy presents challenges due to significant side effects and relatively modest efficacy.

“We don't have excellent treatment options available at the moment in the US,” Kushner said. “However, it is a very exciting time, because there are several new treatments on the horizon.”

In Europe, the entry inhibitor bulevirtide is already approved for HDV treatment, supported by both clinical trial and real-world evidence demonstrating meaningful antiviral activity. The therapy requires daily injections, which Kushner says may limit uptake among some patients but has nonetheless represented an important advance.

She pointed to additional therapies that are also progressing through clinical development, specifically highlighting brelovitug, a monoclonal antibody being developed by Mirum Pharmaceuticals that is currently being evaluated in phase 3 trials across multiple countries, including the United States.

“Just 10 years ago, we had nothing available, so I think the field is seeing an exciting development where we hopefully will have options for our patients who really need it,” Kushner said.

Ghany MG, Pan CQ, Lok AS, et al. AASLD ISDA Practice Guideline on treatment of chronic hepatitis B. 

. Published online November 4, 2025. doi:10.1097/HEP.0000000000001549

MYR Pharmaceuticals. MYR Pharmaceuticals receives Conditional Marketing Authorization by the European Commission for HEPCLUDEX®. August 4, 2020. Accessed March 12, 2026. 

https://www.prnewswire.com/news-releases/myr-pharmaceuticals-receives-conditional-marketing-authorization-by-the-european-commission-for-hepcludex-301105418.html

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 12, 2026. 

Kushner discusses the global burden of hepatitis D, gaps in testing, and emerging therapies reshaping the treatment landscape.

Tatyana Kushner, MD

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