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

Tatyana Kushner, MD

Liver Lineup: Updates & Unfiltered Insights

Liver Lineup: Bepirovirsen and the Push Toward Functional Cure in Hepatitis B

 has gone decades without a finite treatment option, but that may be about to change. On this episode of 

, hosts Nancy Reau, MD, and Kimberly Brown, MD, are joined by Tatyana Kushner, MD, a hepatologist at Weill Cornell Medicine, to discuss bepirovirsen, an investigational antisense oligonucleotide from GSK and Ionis Pharmaceuticals that recently became the first agent to demonstrate functional cure as a phase 3 primary endpoint in chronic hepatitis B (CHB).

Bepirovirsen Phase 3 Data in Chronic Hepatitis B

The conversation centers on data from the B-Well 1 and B-Well 2 trials, presented at the European Association for the Study of the Liver (EASL) Congress and simultaneously published in the New England Journal of Medicine in May 2026. The 2 replicate, double-blind, placebo-controlled trials enrolled 1834 participants across 29 countries with non-cirrhotic CHB who were on stable nucleos(t)ide analogue (NA) therapy and had baseline HBV DNA below 90 IU/mL and HBsAg between 100 and 3000 IU/mL, randomized 2:1 to weekly subcutaneous bepirovirsen 300 mg or placebo alongside standard NA therapy for 24 weeks.

Liver Lineup: HDV Diagnosis, Bulevirtide, and the Delta Pipeline

Liver Lineup: Closing the Gap in Women’s Liver Health

Liver Lineup: Navigating Genetic Testing in Cholestatic Liver Disease

Functional cure at week 72 was achieved in 20% of bepirovirsen-treated patients versus none of the placebo recipients in B-Well 1, and 19% versus 0% in B-Well 2, with response rates climbing further in patients with lower baseline HBsAg — up to 28% among those with baseline HBsAg of 1000 IU/mL or less. Sustained HBV DNA suppression after NA discontinuation, a key secondary endpoint, was reported in 23% of bepirovirsen-treated patients in both studies.

HBsAg Quantification and Patient Selection for Bepirovirsen

Kushner frames HBsAg quantification as the practical starting point for clinicians. She notes that she has begun routinely checking quantitative surface antigen in her own CHB patients, a test she previously considered non-actionable, because it will likely determine eligibility if bepirovirsen is approved. She cites discussion at a Coalition for Hepatitis Elimination conference suggesting roughly 50% to 60% of patients may fall under the HBsAg 3000 IU/mL threshold, though she, Reau, and Brown all note their own clinical experience suggests a lower proportion, complicated by limited access to quantitative, rather than qualitative, assays at some institutions.

Much of the discussion also addresses what functional cure means relative to spontaneous HBsAg loss and continued NA therapy; the group converges on sustained off-treatment HBsAg loss as the accepted endpoint, given its association with reduced HCC and cirrhosis progression risk, while acknowledging open questions about durability beyond the trial window.

Bepirovirsen Dosing, Monitoring, and Safety Considerations

The panel works through practical rollout questions: the drug's weekly injection schedule and potential for at-home administration, and the intensive monitoring likely required in the first 12 weeks given signals for ALT elevation and renal effects. The group agrees cirrhotic and decompensated patients, who were not studied, are unlikely candidates.

Brown highlights a discontinuation rate around 3% in the trials as reassuring relative to older interferon-based regimens, while Kushner cautions that real-world tolerance of ALT flares may differ from the closely monitored trial setting.

What's Next for Bepirovirsen in Hepatitis B Care

The conversation closes on access and uptake — whether primary care practices managing large hepatitis B populations, particularly in Asian American communities, will be positioned to administer and monitor this therapy, or whether care will concentrate in specialized centers. All 3 agree that regardless of uptake, an approval would likely drive renewed attention to hepatitis B screening and treatment linkage, areas where diagnosis and treatment rates in the US remain low.

Bepirovirsen is not yet approved; the FDA has accepted the New Drug Application for priority review and set a PDUFA goal date of October 26, 2026.

Hou J, et al. Phase 3 results of bepirovirsen treatment for chronic hepatitis B virus infection. 

Lok A. A major step toward a cure for hepatitis B infection. 

. 2026;394:2471-2472. doi:10.1056/NEJMe2605575

Brooks A. FDA Grants Bepirovirsen Breakthrough Therapy Designation, Priority Review for Chronic Hepatitis B. HCPLive. April 28, 2026. Accessed July 8, 2026. 

https://www.hcplive.com/view/fda-grants-bepirovirsen-breakthrough-therapy-designation-priority-review-for-chronic-hepatitis-b

Podcasts

Tatyana Kushner, MD, joins Kim Brown, MD, and Nancy Reau, MD, to unpack bepirovirsen's phase 3 data and its implications for HBV care.

Liver Lineup: Updates and Unfiltered Insights

, hosts Kimberly Brown, MD, and Nancy Reau, MD, are joined by Tatyana Kushner, MD, a hepatologist at Weill Cornell Medicine, for a wide-ranging discussion on hepatitis delta virus (HDV), from longstanding barriers to diagnosis to the first US-approved treatment and what comes next in the pipeline.

0:01:30 – Introduction, framing of New York/Chicago as HDV “hotspots” driven by immigrant populations and under-recognized disease burden.

0:05:18 – Historical under-testing for HDV in HBV patients and VA data showing <10% of HBV patients ever receive delta testing despite higher rates of cirrhosis and HCC.

0:07:55 – Discussion of evolving guidelines and anticipation that AASLD will move toward testing all HBsAg-positive individuals at least once for HDV.

0:10:49 – Practical care cascade overview: who to test, HDV antibody followed by HDV RNA, and how to interpret discordant or low-level results.

0:20:13 – Historical treatment approach with pegylated interferon, trial access, and the unmet need in patients excluded from studies or with advanced disease.

0:26:16 – Debate on combining pegylated interferon with bulevirtide versus long-term bulevirtide monotherapy, including tolerability and “finite” versus maintenance strategies.

0:35:11 – Forward-looking segment on bulevirtide approval in the US, its practical use (daily injection, reconstitution), and pipeline agents with promising data.

Kushner opens by reflecting on how dramatically the field's attention to HDV has shifted. For much of her early career, delta hepatitis was treated as an afterthought at national conferences, with little urgency around testing or treatment. Over the past 5 years, growing evidence on rapid disease progression, elevated risk of cirrhosis and hepatocellular carcinoma, and now an approved therapeutic have changed the calculus entirely.

A central theme of the conversation is the persistent gap between how many patients likely have HDV and how many have ever been tested for it. Kushner describes early research she conducted with colleagues in the national VA system showing fewer than 10% of hepatitis B surface antigen-positive patients had ever received a delta test despite measurably more advanced liver disease among those ultimately found to be co-infected. Reau and Brown echo this, noting guidelines have historically tied testing to specific risk factors or abnormal transaminases, a standard both hosts view as too narrow given HDV's clinical consequences.

All 3 clinicians express support for universal testing in all hepatitis B surface antigen-positive individuals. Reau notes AASLD is expected to release updated hepatitis D guidance, and signals her expectation the society will move toward recommending at-least-once screening in all HBsAg-positive patients. The discussion also covers the practical mechanics of the diagnostic cascade, from HDV antibody to reflex HDV RNA, and the logistical hurdles, from send-out testing delays to billing complexities, institutions have faced in trying to implement reflex testing programs.

The episode also serves as an on-the-ground assessment of bulevirtide (Hepcludex), approved by the US Food and Drug Administration in May 2026 for chronic HDV infection. Kushner walks through the administration requirements, including daily self-injection with patient-performed reconstitution, and notes Gilead's decision to formulate the US 8.5 mg dose without refrigeration requirements, a deliberate improvement over the European 2 mg formulation.

She and Reau discuss the practical question of whether to combine bulevirtide with pegylated interferon in appropriate candidates, particularly those with less advanced fibrosis who may be candidates for finite therapy. Recent data showed meaningfully higher off-treatment response rates at the 10 mg dose compared to the 2 mg combination arm, a point that generated notable discussion at the recent EASL conference and the Hepatitis Delta International Network meeting.

Reau draws on her experience running clinical trials including the lonafarnib program, and both she and Brown emphasize the institutional muscle memory built from treating hepatitis C with interferon-based regimens — expertise she argues will be directly relevant as clinicians reintroduce pegylated interferon for select delta patients.

Kushner closes with an overview of the pipeline beyond bulevirtide, highlighting a pair of phase 3 programs: Vir Biotechnology’s study evaluating tobevibart plus elebsiran, a combination of a monoclonal antibody and siRNA, and a study of brilovertug from Bluejay Therapeutics, recently acquired by Mirum Pharmaceuticals. Both have demonstrated higher rates of undetectable HDV RNA in phase 2 results than bulevirtide in comparable timeframes, and both have closed screening. Head-to-head trials against bulevirtide are planned for both programs.

Editors’ note: Relevant disclosures for 

 include AbbVie, Gilead, Salix, Arbutus, and VIR. Relevant disclosures for 

 include Mallinckrodt Pharmaceuticals, Gilead, Salix, Intercept, Ipsen, and Madrigal. Relevant disclosures for 

 include Gilead, Abbvie, GSK, Ipsen, Mirum, and Madrigal.

US Centers for Disease Control and Prevention. Hepatitis D Basics. April 24, 2024. Accessed June 18, 2026. 

https://www.cdc.gov/hepatitis-d/about/index.html

Lange M, Zaret D, Kushner T. Hepatitis Delta: Current Knowledge and Future Directions. Gastroenterol Hepatol (N Y). 2022;18(9):508-520.

Campbell P. Bulevirtide Receives Historic First FDA Approval for Chronic Hepatitis Delta. HCPLive. May 22, 2026. Accessed June 18, 2026. 

https://www.hcplive.com/view/bulevirtide-historic-first-fda-approval-chronic-hepatitis-delta

Tatyana Kushner, MD, joins hosts Brown and Reau to discuss HDV testing gaps, bulevirtide approval, and the emerging delta hepatitis pipeline.

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. 

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.

Tatyana Kushner, MD

Articles