New hepatitis D drug brelovitug marks milestones in late-stage trials
AZURE studies across globe testing injection therapy's safety, effectiveness
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A late-stage clinical trial assessing the safety and effectiveness of Mirum Pharmaceuticals’ brelovitug for adults with chronic hepatitis D has completed enrollment, and is now evaluating the therapy candidate at sites across 12 countries, including the U.S.
The Phase 3 study, called AZURE-1 (NCT06907290), is testing brelovitug against a six-month treatment delay in about 200 people with chronic hepatitis D. Eligible participants were treatment-naïve, meaning they had received no prior treatment for the condition, which is marked by liver inflammation.
Meanwhile, patient screening has been completed in the parallel Phase 3 AZURE-4 trial (NCT07298330), expected to enroll approximately 80 people with chronic hepatitis D who are also treatment-naïve. This randomized trial is evaluating brelovitug against a three-month treatment delay.
“The completion of AZURE-1 enrollment and AZURE-4 screening [represents] important execution milestones as we advance brelovitug through the Phase 3 AZURE program,” Joanne Quan, MD, chief medical officer at Mirum, said in a company press release announcing the developments.
“We look forward to reporting interim data from AZURE-1 in the [coming months] and topline results from AZURE-1 and AZURE-4 in the second half of 2026,” Quan said.
Data from both trials are intended to support an application to the U.S. Food and Drug Administration (FDA) seeking approval for brelovitug. Mirum expects to file such an application and to potentially launch the therapy next year.
Mirum also announced that the first participant has been enrolled in another Phase 3 AZURE study, this one being conducted in Europe. AZURE-2 (NCT07200908), slated to enroll more than 170 people with hepatitis D, will compare brelovitug with bulevirtide. That antiviral treatment is approved for hepatitis D in some countries, though not in the U.S., under the brand name Hepcludex.
‘Very limited’ options available for treating hepatitis D
Hepatitis D is by a virus of the same name, known as HDV. The virus can only infect people who already have hepatitis B because it relies on the hepatitis B virus (HBV) to infect liver cells and multiply.
People infected with both viruses at the same time often experience mild symptoms. However, those who develop hepatitis D after hepatitis B face a higher risk of complications such as cirrhosis, or severe scarring of the liver, and liver failure.
Available treatments often involve interferon-based therapies that stimulate the immune system, along with antiviral medications that are used to control hepatitis B. Even with treatment, however, hepatitis D infection often cannot be fully eliminated.
“HDV is an aggressive disease that progresses quickly and leaves patients with very limited treatment options,” said Tatyana Kushner, MD, an associate professor of medicine at Weill Cornell Medicine in New York City.
Having a well-tolerated single-agent therapy that achieves viral suppression and [lessens] liver inflammation is critical for patients with HDV [hepatitis D virus].
Brelovitug, previously called BJT-778, is an antibody that binds to the hepatitis B surface antigen (HBsAg). This protein is found on both HBV and HDV particles and is required for the viruses to infect liver cells.
By targeting this protein, the therapy, which is administered via subcutaneous, or under-the-skin, injections, is intended to suppress the growth of both viruses. It’s expected to help the immune system control infection, and thereby prevent further liver inflammation and damage.
“Having a well-tolerated single-agent therapy that achieves viral suppression and [lessens] liver inflammation is critical for patients with HDV,” Kushner said. “The progress of these Phase 3 studies brings us closer to potentially delivering a new therapy to patients in urgent need.”
In earlier trial, brelovitug showed strong antiviral activity
Brelovitug was originally developed by Bluejay Therapeutics, which was acquired by Mirum earlier this year, along with the worldwide rights to the therapy. The drug has received breakthrough therapy designation in the U.S. and orphan drug designation and Priority Medicines status in the European Union, all for treating hepatitis D. These regulatory designations are intended to speed the development of treatments for serious diseases with limited options.
According to interim data from a Phase 1/2a clinical trial (ACTRN12623000105640), brelovitug demonstrated strong antiviral activity against HDV, eliminating all detectable signs of the virus from the blood of people with chronic hepatitis B and D.
Treatment also lowered blood levels of alanine aminotransferase (ALT), a marker of liver damage, and showed a favorable safety profile, with redness at the injection site as the most commonly reported side effect.
In AZURE-1, which started dosing earlier this year, participants are randomly assigned to receive either brelovitug 300 mg once weekly, brelovitug 900 mg once monthly, or a six-month delayed therapeutic start. AZURE-4, meanwhile, is evaluating brelovitug in treatment-naïve hepatitis D patients using a similar regimen, but with a three-month delay.
In both studies, those assigned to the delayed treatment regimen receive 300 mg of brelovitug once weekly following the delay period.
The main goals of the studies are to assess the proportion of participants who achieve a virologic response, meaning little or no signs of the virus, combined with the normalization of ALT levels after 24 weeks, or about six months.
According to Quan, “both studies are evaluating a composite [goal] of virologic response and ALT normalization at 24 weeks, aligned with FDA guidance for accelerated approval in HDV, and building on the strong antiviral activity observed in our Phase 2 study.”
Mirum currently markets therapies for other rare liver diseases, including Livmarli (maralixibat) for Alagille syndrome and progressive familial intrahepatic cholestasis. The company also has a pipeline of liver-targeted investigational medicines, including volixibat for primary sclerosing cholangitis and primary biliary cholangitis.
