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

Tatyana Kushner, MD

Brelovitug Offers New Hope for Hepatitis D Treatment

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 

“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.

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

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

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

Videos

Brelovitug achieved the FDA-specified primary endpoint for HDV RNA reduction and normalization of ALT in a phase 2b trial.

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

Brelovitug AZURE-1 Trial Results in Hepatits D Explained, With Tatyana Kushner, MD

Chronic hepatitis D virus (HDV) infection remains one of the most severe and underrecognized forms of viral hepatitis, often accelerating progression to cirrhosis, liver failure, and hepatocellular carcinoma. Despite its clinical impact, HDV continues to be overlooked in routine practice. For patients already living with hepatitis B virus (HBV), coinfection with HDV can dramatically worsen outcomes, yet gaps in awareness, diagnosis, and treatment persist across the care continuum.

, Tatyana Kushner, MD, discussed these challenges alongside new data from the phase 2b portion of the AZURE-1 study evaluating brelovitug, an investigational therapy for chronic HDV infection. While HDV is estimated to affect approximately 2–5% of individuals with HBV globally, she noted prevalence can be significantly higher in certain regions, highlighting important geographic variability.

Brelovitug is an investigational monoclonal antibody targeting HBsAg, designed to neutralize both HBV and HDV

Phase 2b AZURE-1 met its primary endpoint at Week 24, combining virologic response (HDV RNA reduction) and ALT normalization

Virologic response reached 100% with weekly dosing and 75% with monthly dosing, with 0% in the delayed-treatment arm

Treatment was generally well tolerated, with no reported discontinuations and low rates of serious adverse events

Still, even in high-resource settings, screening rates remain strikingly low, with Kushner pointing to data from New York City showing that < 10% of patients with HBV had ever been tested for HDV, underscoring substantial gaps in case identification.

Several factors contribute to these shortcomings. Differences in clinical guideline recommendations ranging from universal screening endorsements by organizations such as the European Association for the Study of the Liver and the World Health Organization to risk-based strategies from the American Association for the Study of Liver Diseases have created variability in clinical practice. Limited provider awareness further complicates diagnosis, sometimes resulting in missed or incorrect testing. As a result, many patients are only identified once they have progressed to advanced liver disease, making management more difficult.

Treatment limitations have historically compounded these challenges, with no therapies currently approved by the US Food and Drug Administration specifically for HDV.

“In the US, there's currently no FDA approved treatment for delta hepatitis, so providers may think ‘Why would we test for this condition if we don't have any currently FDA approved treatments?’,” Kushner said.

The only recommended option, pegylated interferon, has modest efficacy and is frequently associated with significant tolerability issues, leading many patients to decline or discontinue therapy.

Against this backdrop, emerging data for brelovitug signal a potential shift in the HDV treatment landscape. According to results from the phase 2b AZURE-1 study, the therapy met its primary endpoint, demonstrating meaningful antiviral activity in patients with chronic HDV infection. 

Specifically, results showed 100% of patients in the 300 mg once weekly arm and 75% of patients in the 900 mg once every 4 weeks arm achieved virologic response (≥2 log10 reduction in HDV RNA from baseline or undetectable HDV RNA [<LLOQ, TND]), as compared to 0% in the delayed treatment arm. Additionally, the primary composite endpoint of virologic response and alanine aminotransferase (ALT) normalization was achieved in 45% and 35% of patients in the 300 mg QW and 900 mg Q4W arms, respectively, as compared to 0% of patients in the delayed treatment arm.

Kushner emphasized that these findings are particularly encouraging given the unmet need for effective and tolerable options.

Beyond efficacy, early data suggest brelovitug may offer advantages in tolerability compared with interferon-based approaches, which have long been limited by systemic side effects. Additionally, its dosing profile, potentially allowing for weekly or even monthly administration, could represent a meaningful improvement in convenience and adherence compared with more burdensome regimens.

While additional data and regulatory review are still needed, the AZURE-1 findings highlight growing momentum in HDV research. As awareness and screening efforts evolve in parallel with therapeutic innovation, clinicians may be better equipped to identify and manage this historically underrecognized disease.

US Centers for Disease Control and Prevention. Hepatitis D Basics. April 24, 2024. Accessed April 28, 2026. 

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 28, 2026. 

Brelovitug met the primary endpoint for virologic response and ALT normalization in the phase 2b portion of the AZURE-1 trial.

New Phase 2b AZURE-1 Data Signal Progress in Chronic Hepatitis D Treatment, With 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.

“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.”

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

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.

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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