Redwood City, Calif-based Bluejay Therapeutics, announced last week it had enrolled the first patient for its phase 3 study, AZURE-2, which will examine its investigational monoclonal antibiody, brelovitug, against bulevirtide (Hepcludex)—currently the only approved treatment for chronic hepatitis D (CHD) outside the US. This marks the industry's first phase 3 head-to-head trial comparing an investigational therapy against bulevirtide.
Study Specifics
AZURE-2 is a randomized, controlled study evaluating brelovitug monotherapy (300 mg subcutaneous injection self-administered by participants weekly at home) compared with Hepcludex (bulevirtide) in adults with CHD. The primary endpoint is the proportion of participants who achieve a composite response at week 48, defined as undetectable hepatitis D virus RNA together with normalization of alanine aminotransferase (ALT). Elevated ALT levels are a marker of liver cell inflammation, which drives the development of liver cirrhosis and liver cancer.
Earlier this year, Bluejay’s brelovitug received FDA Breakthrough Therapy designation for the treatment of CHD. The company’s AZURE-1 study, which was initiated in March 2025, has been enrolling in the US and other countries around the world. The AZURE-1 trial is powered to detect superiority of brelovitug treatment compared with delayed treatment.
“The primary endpoints of the AZURE-1 and AZURE-2 trials include a composite measure of viral response and ALT normalization. Evidence from large cohort studies in hepatitis B has shown an association between delayed ALT normalization and increased risk of liver disease progression and liver cancer,” Bluejay Therapeutics CMO Nancy Shulman, MD, said in a statement.1
About the Treatment
Brelovitug is an investigational, highly potent, pan-genotypic, fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets the surface antigen (anti-HBsAg) on both the hepatitis D virus (HDV) and the hepatitis B virus (HBV). Brelovitug offers weekly self-administered injections at home compared to daily injections required with bulevirtide.
Brelovitug is designed to neutralize and remove hepatitis B and hepatitis D virions and deplete HBsAg-containing subviral particles, which gives brelovitug a potentially advantageous safety profile and makes it a potentially efficacious treatment for chronic hepatitis D (CHD), a condition with urgent unmet medical need. In addition, brelovitug has shown immunomodulatory functions in chronic hepatitis B (CHB) patients, which may help to reconstitute antiviral immunity and contribute to functional cure for CHB when combined with other agents.
What You Need to Know
Bluejay Therapeutics has launched AZURE-2, the first phase 3 study directly comparing its investigational antibody brelovitug with bulevirtide (the only approved treatment for chronic hepatitis D outside the US).
Brelovitug, a weekly self-administered monoclonal antibody, targets both HBV and HDV, offering a potentially more convenient and safer option than bulevirtide’s daily injections.
Chronic hepatitis D is the most severe form of viral hepatitis with few approved treatments worldwide, and brelovitug has FDA Breakthrough Therapy designation, highlighting its promise to address this gap.
Chronic Hepatitis D Health Burden
Hepatitis D can be a very severe infection, and it is characterized as a satellite virus as it only infects people who have hepatitis B (HBV). According to the Centers for Disease Control and Prevention,coinfection can happen when people contract both HBV and HDV simultaneously, and it can typically cause health problems up to even liver failure, but it is not typically chronic in nature.2
“Chronic hepatitis D is the most severe form of viral hepatitis, yet it remains underserved, with limited or no approved treatment options in most countries,” Shulman said.1
References
1. Bluejay Therapeutics Enrolls First Patient in AZURE-2 Global Phase 3 Clinical Trial Evaluating Brelovitug (BJT-778) Compared to Hepcludex (R) (Bulevirtide) for Chronic Hepatitis D. Bluejay Therapeutics press release. September 4, 2025. Accessed September 8, 2025.
https://bluejaytx.com/bluejay-therapeutics-enrolls-first-patient-in-azure-2-global-phase-3-clinical-trial-evaluating-brelovitug-bjt-778-compared-to-hepcludex-r-bulevirtide-for-chronic-hepatitis-d/
2. Hepatitis D Basics. CDC. April 24, 2024. Accessed September 4, 2025.
https://www.cdc.gov/hepatitis-d/about/index.html
