Mirum Pharmaceuticals said its experimental hepatitis D treatment brelovitug met the main goal in AZURE-4, its second Phase 3 study of the drug. Results from AZURE-4, together with an earlier Phase 3 study, are intended to support a U.S. application for approval.
The company also presented longer-term data at a liver-disease meeting, reporting that viral and liver-enzyme responses generally improved with continued treatment, including among some patients with advanced cirrhosis.
AZURE-4 results
- The global study enrolled 113 patients with chronic hepatitis delta virus (HDV) who had not previously been treated. More than half had cirrhosis, about half had high baseline levels of HDV, and average baseline ALT—a marker of liver inflammation—was 122 U/L.
- Patients received either 300 mg of brelovitug weekly by self-injection, 900 mg every four weeks, or delayed treatment starting at Week 12.
- At Week 24, the primary endpoint—a combined measure of a substantial reduction in HDV or undetectable virus and normalization of ALT—was reached by 59% of patients on the weekly dose and 44% on the four-week schedule. No patients in the delayed-treatment group reached it. Both comparisons with delayed treatment had p-values of 0.0001 or lower.
- The drug was described as well tolerated, with no new safety signals. Flu-like illness was the most common adverse event, affecting 17.2% of the weekly-dose group and 18.5% of the four-week group; most cases followed the first dose. Injection-site reactions were reported in 1.7% and 7.4%, respectively.
Longer-term findings and next step
- Across the two Phase 3 studies, the reported Week 24 combined-endpoint rates were 56% and 45% in AZURE-1, compared with 59% and 44% in AZURE-4, for the two dose schedules. Neither study’s delayed-treatment group had patients reach the endpoint.
- Phase 2 results presented at the meeting showed continued responses with longer treatment. In a small 15-patient cirrhosis group treated for 108 weeks, all patients reached the combined endpoint; 73% had undetectable HDV. Other small Phase 2 groups also showed ongoing viral and ALT responses at 48 weeks.
- Mirum plans to submit a Biologics License Application for brelovitug. The announcement does not provide a submission timeline.
AZURE-4 is the second of the two Phase 3 studies Mirum says will form the basis of its U.S. registration package. Brelovitug remains investigational; the reported results are clinical-trial findings, not an approval.