The investigational monoclonal antibody mirikizumab was more effective in inducing and maintaining clinical remission in patients with moderate to severe ulcerative colitis (UC) compared with placebo, according to two phase III randomized trials.

Among over 1,200 patients in the LUCENT-1 induction trial, 24.2% of those who received mirikizumab experienced clinical remission at week 12 compared with 13.3% of those in the placebo group (P<0.001), reported Geert D’Haens, MD, PhD, of Amsterdam University Medical Centers in the Netherlands, and colleagues.

In the LUCENT-2 maintenance trial, which included 544 patients with a response to mirikizumab, 49.9% versus 25.1%, respectively, experienced clinical remission at week 40 (P<0.001), they noted in the New England Journal of Medicine.

Secondary endpoints, including clinical response, endoscopic remission, and improvement in bowel movement urgency, were also met.

“Many patients with ulcerative colitis consider control of bowel movements to be more important than rectal bleeding or stool frequency,” D’Haens and team pointed out.

D’Haens and colleagues said that current therapies for UC are limited by increased risks of infection or cancer, non-response to primary therapy, or loss of clinical benefit over time. Mirikizumab, a humanized IgG4-variant monoclonal antibody that binds to subunit p19 of interleukin-23 (IL-23), showed efficacy in a phase II trial of patients with UC.

“This class of drugs seems quite promising for the treatment of both ulcerative colitis and Crohn’s disease,” Andres Yarur, MD, of Cedars-Sinai Medical Center in Los Angeles, told MedPage Today.

There are other drugs for UC that work on subunit p19 of IL-23 either on the market or nearing approval, he noted. “We still don’t know if these drugs are equivalent or not. They seem to be equivalent, but we need more experience with a drug in the real world to try to understand not only how good they work, but also how they compare to each other and to other drugs.”

Mirikizumab is approved in Japan, according to its manufacturer, Eli Lilly. However, the FDA issued a complete response letter to the company, turning down its attempt to get approval in the U.S. for the treatment of UC. Lilly has said that this stems from issues the FDA has with manufacturing processes for the drug, rather than with the clinical data, safety, and proposed labeling in the marketing application.

LUCENT-1 included 1,281 patients who were randomized 3:1 to receive 300-mg intravenous mirikizumab or placebo every 4 weeks for 12 weeks. Mean age was 41-43, and 56-61% were men.

Clinical remission in LUCENT-1 was defined as a modified Mayo stool frequency subscore of 0 (on a scale from 0 to 3) or a stool frequency subscore of 1 with a decrease of at least 1 point from baseline, a rectal bleeding subscore of 0, and an endoscopic subscore of 0 or 1 excluding friability.

LUCENT-2 included 544 patients who had responded to mirikizumab in LUCENT-1 and were randomly assigned 2:1 to receive either 200-mg mirikizumab or placebo every 4 weeks for 40 weeks. Maintenance of clinical remission was defined as clinical remission in patients who had had clinical remission with mirikizumab in the induction trial.

Patients who did not have a response in the induction trial were allowed to receive open-label mirikizumab during the first 12 weeks of the maintenance trial as an extended induction.

At 40 weeks of maintenance, 97.8% of patients who were in clinical remission were no longer taking glucocorticoids. However, patients in the placebo group of the maintenance trial lost some of the improvement they had gained during the induction trial.

The incidence of adverse events during both trials was similar between the mirikizumab and placebo groups. Nasopharyngitis and arthralgia were more frequent with mirikizumab than with placebo. Among the 1,217 patients treated with mirikizumab during controlled and uncontrolled periods of the trials, 15 had an opportunistic infection (including six with herpes zoster infection) and eight had cancer (including three with colorectal cancer). Among the patients who received placebo in the induction trial, one had herpes zoster infection, and none had cancer.

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