Mirum Pharmaceuticals has kept its clinical winning streak alive in hepatitis D, meeting the primary endpoint in another late-stage trial of its antiviral monoclonal antibody brelovitug. The success sets up the biotech to challenge Gilead Sciences.
The Azure-4 study showed that 59% of patients who self-administered a weekly injection of 300 mg brelovitug achieved a virologic response and aminotransferase (ALT) normalization after 24 weeks, while 44% of those on a monthly 900 mg dose saw the same result. In contrast, no patients in a third arm—who didn't receive brelovitug treatment during the 12 weeks—hit this endpoint.
The 113 patients in the study had substantial hepatitis B burden and had not previously been treated for the disease. More than half had cirrhosis and high levels of viral RNA, while the group’s average ALT levels, which mark inflammation in the liver, were well above normal.
Hepatitis D is the most severe form of the disease, affecting as many as 4% of patients who also have hepatitis B. Brelovitug binds to the hepatitis B antigen, which also exists on the delta form of the virus. The therapy has breakthrough designation from the FDA for chronic hepatitis D and orphan drug designation for active hepatitis D.
The Azure-4 results follow another successful phase 3 readout back in September for a study called Azure-1, in which Mirum also hit the primary endpoints of virologic response and ALT normalization with the same doses and administration timelines. That trial saw 56% and 45% virologic response rates, respectively, for the 300 mg and 900 mg cohorts.
Mirum picked up brelovitug in the $620 million acquisition of Bluejay Therapeutics last year. Alongside mid-stage trials stretching out to 48 weeks and 108 weeks, Mirum plans to take brelovitug results to the FDA in the first half of 2027, aiming for commercial launch by the end of the year.
“Together with the favorable safety and tolerability profiles observed across both Azure studies and the deepening responses observed with longer-term treatment in our phase 2 studies, we believe these results support the potential of brelovitug as a potent, single-agent treatment for chronic HDV and our planned biologics license application submission in the first half of 2027,” Nancy Shulman, M.D., executive vice president of clinical development at Mirum, said in a Nov. 10 release.
Gilead already received its own FDA nod in May for the chronic hepatitis D drug Hepcludex, which is a daily injectable treatment with a 48% response rate on the combined endpoint of response rate and ATL normalization. The company had met with complications due to manufacturing and delivery concerns prior to gaining the regulatory green light.
While Hepcludex is approved for patients with chronic hepatitis D without cirrhosis, Mirum could potentially stand out as an option for those with more severe forms of the disease. Vir Biotechnology is also in the running with an ongoing phase 3 trial combining the drugs elebsiran and tobevibart in patients with hepatitis D.
Leerink analysts had previously named Mirum’s enrollment of severe patients as “a key point of differentiation” versus Vir’s combination, adding that its low rates of flu-like symptoms are another edge.