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There were higher percentages of patients treated with mirikizumab that had clinical remission at week 12 of the induction trial compared to the placebo group. This was also true at week 40 of the maintenance trial.
A team, led by Geert D’Haens, MD, PhD, compared mirikizumab to placebo in both an induction trial and a maintenance trial involving patients with moderately to severely active ulcerative colitis.
In phase 2 trials, mirikizumab, which is a p19-directed antibody against interleukin-23, has shown promise in treating patients with ulcerative colitis.
The investigators reported results from a pair of phase 3, randomized, double-blind, placebo-controlled trials in adults with moderately to severely active ulcerative colitis.
In the induction trial, each participant was treated with either mirikizumab 300 mg or placebo intravenously every 4 weeks for 12 weeks and in the maintenance trial, each patient with a response to mirikizumab induction therapy was treated with mirikiziumab 200 mg or placebo subcutaneously every 4 weeks for an additional 40 weeks.
The investigators sought primary endpoints of clinical remission at week 12 in the induction trial and week 40 in the maintenance trial. They also looked at major secondary endpoints of clinical response, endoscopic remission, and improvement in bowel-movement urgency.
Patients who did not have a response in the induction trial were then allowed to be part of the open-label mirikiziumab during the first 12 weeks of the maintenance trial as an extended induction.
The induction trial included 1281 patients, 544 of which had a response to mirikiziumab and were entered into the maintenance trial.
There were higher percentages of patients treated with mirikizumab that had clinical remission at week 12 of the induction trial compared to the placebo group (24.2% vs. 13.3%; P <0.001). This was also true at week 40 of the maintenance trial (49.9% vs. 25.1%; P <0.001).
The criteria for all of the major secondary endpoints were met in both trials.
In the safety analysis, adverse events such as nasopharyngitis and arthralgia were more frequently reported in the mirikizumab group compared to placebo.
Of the 1217 patients in the mirikizumab group during the controlled and uncontrolled periods, 15 had opportunistic infections, including 6 participants with herpes zoster infections, and 8 had cancer, including 3 with colorectal cancer.
In the induction trial placebo group, 1 participant had a herpes zoster infection and there were no cases of cancer.
“Mirikizumab was more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis,” the authors wrote. “Opportunistic infection or cancer occurred in a small number of patients treated with mirikizumab.”
In April, the US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for mirikizumab, citing issues related to the proposed manufacturing of the treatment.2
The CRL, which was issued for the Biologic License Application (BLA) by Eli Lilly and Company, did not cite any concerns about the clinical data package, safety, or label for the medicine.
1. D’Haens, G., Dubinsky, M., Kobayashi, T., Irving, P. M., Howaldt, S., Pokrotnieks, J., Krueger, K., Laskowski, J., Li, X., Lissoos, T., Milata, J., Morris, N., Arora, V., Milch, C., Sandborn, W., & Sands, B. E. (2023). Mirikizumab as induction and maintenance therapy for ulcerative colitis. New England Journal of Medicine, 388(26), 2444–2455. https://doi.org/10.1056/nejmoa2207940
2. U.S. Food and Drug Administration Issues Complete Response Letter for mirikizumab. Eli Lilly and Company. (2023, April 13). Retrieved April 13, 2023, from https://investor.lilly.com/news-releases/news-release-details/us-food-and-drug-administration-issues-complete-response-1