Mirum Pharmaceuticals’ Brevlovitug Hits Phase III Endpoint in Hepatitis Delta Study

Mirum Pharmaceuticals (NASDAQ:MIRM) reported positive top-line results from the Phase III portion of its AZURE-1 study evaluating brelovitug for chronic hepatitis delta, saying the investigational antibody met its primary endpoint at 24 weeks and showed a favorable tolerability profile.

The company also provided 48-week data from the Phase II-B portion of AZURE-1, discussed plans for a biologics license application submission in the first half of next year, and outlined commercial preparations for brelovitug and its newly FDA-approved medicine Atebrioz for fibrodysplasia ossificans progressiva, or FOP.

AZURE-1 Meets Primary Endpoint

AZURE-1 enrolled 153 patients globally with chronic hepatitis delta, a condition that occurs alongside hepatitis B infection and can progress rapidly to cirrhosis, liver cancer and liver failure. The Phase III study evaluated weekly 300 mg subcutaneous brelovitug, a 900 mg every-four-weeks regimen, and a delayed-treatment control arm that crossed over to weekly treatment at week 24.

Nancy Shulman, Mirum’s executive vice president of clinical development, said the study population included patients with substantial disease burden. At baseline, 41% had cirrhosis, 20% had clinically significant portal hypertension, and 18% had alanine aminotransferase, or ALT, levels greater than five times the upper limit of normal.

For the 300 mg once-weekly regimen, 56% of patients achieved the study’s combined primary endpoint of virologic response and ALT normalization at week 24, compared with zero patients in the delayed-treatment group. Virologic response was observed in 86% of weekly-dose patients, versus zero in the control arm, while 63% achieved ALT normalization, also compared with zero in the delayed-treatment arm.

Additionally, 25% of patients receiving the weekly dose achieved hepatitis delta virus RNA below the assay’s lower limit of quantification of 10 IU/mL, including 17% who reached target-not-detected status, according to the company.

Shulman said brelovitug was well tolerated, with no treatment-related serious adverse events, Grade 3 adverse events or discontinuations reported. The company also cited low rates of flu-like symptoms.

Longer-Term Data and Regulatory Plans

The Phase II-B portion of AZURE-1 included the first 53 patients enrolled in the broader study. At 48 weeks, Mirum said patients continued to show deeper viral suppression and increasing ALT-normalization rates with ongoing treatment.

During the question-and-answer session, Shulman said the company has observed continued reductions in ALT beyond the upper limit of normal. She also said there appeared to be no difference in response between cirrhotic and non-cirrhotic patients in the Phase III population.

Mirum expects top-line results from AZURE-4, its second Phase III study of brelovitug, in the fourth quarter. Chief Executive Officer Chris Peetz said the company is aligned with the FDA on including both AZURE-1 and AZURE-4 in its planned filing and remains on track for a biologics license application submission in the first half of next year.

The AZURE studies include 96 weeks of treatment, followed by an optional open-label extension of up to three additional years. Shulman said the company intends to assess rates of disease progression over five years against historical controls.

Commercial Outlook for Hepatitis Delta

Peter Radovich, Mirum’s president and chief operating officer, said the company estimates that approximately 15,000 U.S. hepatitis delta patients are diagnosed, insured and under care today. He said testing for hepatitis delta has historically been low and that much of the disease burden is outside academic medical centers, including infectious disease, primary-care and community settings.

Mirum has deployed roughly 10 field personnel to support disease-state awareness and scientific exchange around hepatitis delta testing and treatment, Radovich said. The company believes the identified patient population is sufficient to support its updated expectation for brelovitug peak sales of at least $1 billion, with further diagnosis potentially representing upside.

Management said the revised sales outlook reflects confidence in brelovitug’s single-agent profile and pricing assumptions influenced by the U.S. launch pricing of Hepcludex. Mirum expects brelovitug to be used as chronic therapy.

The company said it is developing an autoinjector for brelovitug, though its anticipated launch presentation would be a liquid-in-vial product that does not require reconstitution. The 300 mg dose has a volume of 2 mL.

Atebrioz Approval and Launch Preparation

Separately, Mirum said the FDA recently approved Atebrioz tablets to reduce the volume of total new heterotopic ossification in adults and pediatric patients age 12 and older with FOP. Peetz said Atebrioz is Mirum’s fourth commercial medicine.

Radovich described Atebrioz as a once-daily oral ALK2 inhibitor targeting a disease-driving pathway in FOP. Mirum plans to launch the medicine in October and expects revenue to begin in the first quarter of 2027. The company said the launch will use its existing rare-genetics commercial team, which already supports CTEXLI and CHOLBAM.

Mirum said it plans to make its final Atebrioz pricing decision at launch and expects the price to be in the range of Pasatru.

About Mirum Pharmaceuticals (NASDAQ:MIRM)

Mirum Pharmaceuticals, Inc is a biopharmaceutical company focused on developing and commercializing medicines for rare diseases of the liver and gastrointestinal system. The company’s work centers on conditions involving impaired bile acid transport and cholestasis, which can cause serious liver damage and debilitating symptoms such as itching.

Mirum’s primary commercial product is Livmarli (maralixibat), an oral ileal bile acid transporter inhibitor. In the United States, Livmarli is approved to treat cholestatic pruritus associated with Alagille syndrome and progressive familial intrahepatic cholestasis in eligible pediatric patients.