Brelovitug met the primary endpoint for virologic response and ALT normalization in the phase 2b portion of the AZURE-1 trial.
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.
In an interview with HCPLive, 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.
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.
Editors’ Note: Kushner reports relevant disclosures with Gilead, Abbvie, GSK, Ipsen, Mirum, and Madrigal.
