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The biologic drug mirikizumab performed significantly better than placebo in Phase 3 trials, LUCENT-1 and LUCENT-2, for the induction and maintenance therapy of moderate to severe ulcerative colitis (UC), according to a study published late last month in the New England Journal of Medicine. Participants receiving mirikizumab in the induction phase of the study achieved UC remission nearly twice as often as those receiving a placebo.
Mirikizumab belongs to a class of antibody drugs targeting interleukin-23 (IL-23) and, more specifically to subunit p19 of interleukin-23 IL-23 is a pro-inflammatory factorassociated with inflammation in UC. Mirikizumab is not yet approved in the U.S. In April, the FDA declined to approve mirikizumab, citing manufacturing issues.
Part one of the trial evaluated mirikizumab for induction therapy. With UC, induction is a period in which patients have few if any active symptoms of the disease. Three out of every four participants were assigned to received mirikizumab; the others received placebo. Treatment with a 300-mg dose of mirikizumab or placebo was administered intravenously every four weeks over a 12-week period. Those reaching remission on mirikizumab in part one could be enrolled in part two, which was designed to evaluate the efficacy of the drug as maintenance therapy. In this phase, participants were randomized to receive mirikizumab 200 mg or placebo subcutaneously every four weeks for 40 weeks.
The investigators, led by Geert D’Haens, M.D., Ph.D., of the Amsterdam University Medical Centers, analyzed the clinical remission and response rates at the end of each part of the trial (week 12 and week 40). In addition, safety data was collected to compare with previous mirikizumab studies and ensure continued safety.
Nearly 1,300 patients were included in part one of the trial; 24.2% of the mirikizumab recipients achieved clinical remission at 12 weeks compared with 13.3% of those who received a placebo.
Of the 1,300 patients originally enrolled, 544 participated in the second part of the trial that extended to week 40. Mirikizumab was again more effective in keeping UC in remission with 49.9% of mirikizumab users in remission compared with 25.1% of the placebo group.
From a safety perspective, mirikizumab patients exhibited similar side effects to those seen in previous trials. Common cold symptoms and mild joint pain occurred more frequently in those receiving mirikizumab than placebo. Potential severe side effects of mirikizumab identified in the trial included infection and cancer, both likely due to the drug’s effects on the immune system.
The trial was funded by Eli Lilly. The company is also conducting clinical trials to evaluate mirikizumab as a potential treatment for Crohn’s disease.