A phase 3 trial of Mirum Pharmaceuticals’ chronic hepatitis delta virus drug candidate has hit its primary endpoint, furthering the biotech’s efforts to enter a space recently colonized by Gilead Sciences.
The phase 3 portion of Mirum’s Azure-1 clinical trial randomized patients to receive one of two doses of brelovitug or to delay treatment for 24 weeks. Patients received brelovitug, an antibody that binds to a hepatitis surface antigen, as subcutaneous injections of 300 mg once weekly or 900 mg every four weeks. At Week 24, both regimens beat the delayed treatment arm on the trial’s primary endpoint.
“Net-net, these data set brelovitug up to be commercially differentiated in a nascent market, which we expect will grow over time as testing rates improve,” Leerink Partners analysts said in a note to investors.
The primary endpoint combined virologic response and normalization of ALT, a marker of inflammation in the liver. Mirum reported primary endpoint response rates of 56% on 300 mg, 45% on 900 mg and 0% in the delayed treatment control arm. About 85% of patients on brelovitug had a virologic response. ALT normalized in 63% of people in the 300-mg arm and 54% of patients in the 900-mg cohort.
As Leerink analysts noted, the results look better than phase 2b data that Mirum shared in April. The phase 2b portion of Azure-1 included the first 53 patients enrolled in the trial. At Week 24, the phase 2b primary endpoint was met by 45% of people in the 300 mg arm and 35% in the 900 mg cohort.
The biotech shared Week 48 phase 2b data alongside the phase 3 results. Response rates improved over time, rising to 55% in both cohorts by Week 48. The increases reflect rising rates of ALT normalization in both arms, plus an uptick in the 900-mg virologic response rate.
Mirum chose the composite primary endpoint because “a virologic response alone does not necessarily mean that liver inflammation has resolved,” Nancy Shulman, M.D., executive vice president of clinical development at Mirum, said on a conference call with analysts. Liver inflammation is the key driver for progression to fibrosis, cirrhosis and cancer, Shulman added.
Gilead recently won FDA approval for its daily injectable Hepcludex based on a 48% response rate on the combined efficacy endpoint. Vir Biotechnology is running a phase 3 trial of elebsiran and tobevibart in combination. Leerink analysts 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.
Mirum expects to share phase 3 data from another trial, Azure-4, in the fourth quarter. If that trial hits, the biotech could seek FDA approval for brelovitug in the first half of next year and bring it to market by the end of 2027. Mirum acquired the asset through the $620 million Bluejay Therapeutics buyout that it struck late last year.