Mirum Pharmaceuticals announced on November 10 that brelovitug, its antibody against hepatitis B surface antigen, met the primary endpoint in AZURE-4, the second of two Phase 3 studies that will form the basis of its United States registration package in chronic hepatitis delta virus, or HDV. The trial enrolled 113 treatment-naive patients, randomised 2:1:1 to self-administered subcutaneous brelovitug at 300 mg once weekly, 900 mg once every four weeks, or delayed treatment starting at week 12. The population carried substantial disease burden: 53 percent had cirrhosis, about half had baseline HDV RNA above 6 log10 IU/mL, and mean baseline ALT was 122 U/L.
At week 24, 59 percent of the weekly-dose group (n of 58) and 44 percent of the monthly-dose group (n of 27) achieved the combined endpoint of virologic response and ALT normalisation, compared with 0 percent in the delayed-treatment arm, at p of 0.0001 or less for both comparisons. Virologic response alone was 95 percent and 96 percent in the two dose groups. The result replicates AZURE-1, reported in September, where the same combined endpoint was met by 56 percent and 45 percent of the two dose groups. Longer-term Phase 2 data presented at the American Association for the Study of Liver Diseases meeting showed responses deepening with continued treatment. Mirum said no new safety signals were identified, with flu-like illness the most common adverse event in the reports of the data. Brelovitug holds FDA Breakthrough Therapy designation for chronic HDV and Orphan Drug designation for active HDV infection.
Mirum plans to submit a Biologics License Application to the FDA in the first half of 2027, with a potential United States commercial launch in the fourth quarter of 2027 if approved. The company acquired brelovitug in its 620 million dollar acquisition of Bluejay Therapeutics last year, according to Fierce Biotech. The competitive field is filling in: Gilead’s Hepcludex, a daily injection, received its FDA approval in May with a 48 percent response rate on the combined endpoint and is approved for patients without cirrhosis, while Vir Biotechnology’s elebsiran and tobevibart combination succeeded in its first pivotal study, reported on this site on November 8, with two further pivotal trials due early next year. Mirum’s differentiation case is that its single-agent antibody was tested in, and worked in, a population where more than half already had cirrhosis.