Multiple trials aimed at securing US approval of brelovitug for hepatitis D
It's also being compared against medication approved in some other countries
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Mirum Pharmaceuticals is making progress with a quartet of late-stage clinical trials designed to test brelovitug, the company’s experimental therapy for chronic hepatitis D.
These trials aim not only to establish whether brelovitug is effective for treating hepatitis D, but also to gather data on how the investigational therapy compares with a medication approved as standard of care in some countries, though notably not the U.S.
“Mirum was compelled to bring brelovitug for [hepatitis D] into our pipeline because we saw an opportunity to leverage our deep expertise in rare liver disease to help advance a potential new treatment for this overlooked patient population,” Joanne Quan, MD, Mirum’s chief medical officer, told Liver Disease News in a written Q&A.
Brelovitug entered Mirum’s pipeline through the acquisition of Bluejay Therapeutics, its original developer.
Brelovitug designed to block key protein
Hepatitis D, caused by the hepatitis D virus (HDV), is a rare liver infection that can only develop in people who are already infected with the hepatitis B virus (HBV), a more common liver infection that causes hepatitis B.
Co-infection with both viruses “is the most severe form of viral hepatitis [inflammation] and remains a significant unmet need,” Quan said, noting that there currently are no approved treatments for hepatitis D in the U.S.
“The disease can progress quickly to cirrhosis [irreversible liver scarring], liver cancer and liver-related death, underscoring the need for therapies that address both viral activity and liver inflammation [hepatitis],” Quan added.
Brelovitug is an antibody-based therapy designed to block the hepatitis B surface antigen (HBsAg), a protein produced by the HBV that is essential for both viruses’ multiplication and infection of liver cells.
“HBsAg is a key protein for the hepatitis B virus,” Tatyana Kushner, MD, an associate professor of medicine at Weill Cornell Medicine, told Liver Disease News. “The hepatitis D virus uses this protein in order to form infectious particles and enter new liver cells. … If we can have therapies that eliminate HBsAg, then that would halt HDV from causing infection and damage to the liver.”
Brelovitug, administered via under-the-skin injections, received breakthrough therapy designation for hepatitis D in the U.S. and priority medicines and orphan drug designations in the European Union. These statuses are intended to accelerate the therapy’s clinical development and regulatory review.
Top-line data from 2 trials expected in 2026 and 2029
Mirum is currently running the AZURE program, comprised of four late-stage clinical trials of brelovitug, which “is designed to answer different questions that are important for both regulators and clinicians,” Quan said.
The Phase 2b/3 AZURE-1 study (NCT06907290) and the Phase 3 AZURE-4 trial (NCT07298330) will form the basis for brelovitug’s approval in the U.S. Both global studies are testing the therapy against several months of delayed treatment in adults with previously untreated chronic hepatitis D.
“With a delayed treatment arm, there is a natural ‘control’ population where you can compare the efficacy of brelovitug to not being treated,” Kushner said.
AZURE-1 has recently completed enrollment, while AZURE-4 has concluded participants’ screening. Top-line data are expected in 2026 and 2029, respectively.
In parallel, the ongoing Phase 3 AZURE-2 study (NCT07200908) and Phase 2b/3 AZURE-3 trial (NCT07454837) aim to gather data on how brelovitug compares with bulevirtide, an antiviral therapy approved for hepatitis D in Europe and other markets under the brand name Hepcludex. Both studies are being conducted in Europe.
My hope is that reaching the primary [goal] in the majority of patients without significant adverse events would lead to accelerated approval, as treatments are desperately needed in our patients living with HDV.
AZURE-2 is recruiting previously untreated chronic hepatitis D adult patients who will be randomly assigned to one of the two therapies. AZURE-3 is enrolling adult patients who have been taking bulevirtide for at least six months and who will be switched to brelovitug, either immediately or after about 1.5 years.
“Given that bulevirtide is a standard of care treatment currently in Europe and will hopefully also become available in the United States in the future, comparing outcomes directly between these two treatments … will provide data on comparative efficacy, but also may identify patients who respond differently to one treatment versus the other,” Kushner said.
Quan added that “these studies help us understand how brelovitug may compare to or be used in place of bulevirtide and are important for informing its potential role for patients who may have access to both drugs.”
In three of the trials, the main goal is to assess how well brelovitug can induce a composite response defined by a decrease in blood levels of HDV genetic material and a liver damage marker called alanine aminotransferase (ALT).
“The composite [measure] has been used across HDV clinical trials and takes into account the effect of the medication on both viral decline (HDV) and liver inflammation (as reflected by ALT), with the recognition that both aspects are important to liver health and outcomes,” Kushner said. “[A reduction] in these parameters will likely be associated with improvement in quality of life, as we know from other liver conditions that liver inflammation can lead to worse quality of life.”
In addition to the composite goal, Kushner hopes that many trial participants will reach undetectable levels of HDV genetic material — “an even more ambitious outcome” — and experience “improvement in other clinically relevant outcomes,” such as a reduction in liver stiffness (a proxy of liver scarring) and gains in quality of life.
“My hope is that reaching the primary [goal] in the majority of patients without significant adverse events would lead to accelerated approval, as treatments are desperately needed in our patients living with HDV,” Kushner added.
