FDA approves mirikizumab, a promising induction and maintenance therapy for ulcerative colitis

The U.S. Food and Drug Administration (FDA) approved mirikizumab, on October 26, 2023, a highly effective new treatment for ulcerative colitis (UC), offering a new option to patients battling this chronic and debilitating inflammatory bowel disease.

This therapy offers a safe and effective treatment option for patients with moderate-to-severely active UC who have yet to achieve rapid and lasting improvements on currently available therapies. Unlike existing treatments for UC, mirikizumab also offers relief from a key symptom—bowel urgency—that greatly impacts patients' quality of life.

Ulcerative colitis affects millions of people worldwide. The induction and maintenance of remission are critical goals in the management of UC. However, existing therapies may not provide sufficient efficacy or patients may have trouble tolerating them.

"Mirikizumab is the first antibody targeting p19/interleukin-23 to be approved for the treatment of ulcerative colitis. Its performance in both induction and maintenance phases of the clinical trials is truly impressive," said Bruce Sands, MD, MS, senior author of the clinical trial study published in the New England Journal of Medicine (NEJM). Dr. Sands is Chief, Dr. Henry D. Janowitz Division of Gastroenterology, Mount Sinai Health System, and the Dr. Burrill B. Crohn Professor of Medicine, Icahn School of Medicine at Mount Sinai. Dr. Sands is also a paid consultant for Lilly U.S., LLC.

"The Lucent program was the first clinical trial program that addressed bowel urgency in a meaningful way," said Marla C. Dubinsky, MD, co-author of the NEJM study, Co- director, Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center, and Professor of Pediatrics, and Medicine, Icahn Mount Sinai. "It is one of the most burdensome patient-reported symptoms, and a drug that achieves bowel urgency remission is an outcome of great importance to our patients with UC."

As published in NEJM, mirikizumab demonstrated exceptional results in both the induction and maintenance arms of the phase 3, randomized, double-blind, placebo-controlled trials in adults with moderately-to-severely active UC.

Induction Phase (LUCENT-1 Trial)

During the induction phase, the LUCENT-1 trial evaluated the efficacy of mirikizumab in inducing clinical remission at week 12 in patients with moderate to severely active UC.

The study enrolled 1,281 patients who were randomized 3:1 to receive intravenous 330mg mirikizumab or placebo every four weeks for 12 weeks. A significantly greater proportion of mirikizumab-treated patients achieved clinical remission at week 12 (mirikizumab: 24.2%; placebo: 13.3%; p<0.001).

Maintenance Phase (LUCENT-2 Trial)

In the maintenance phase, the LUCENT-2 trial assessed the potential of mirikizumab to maintain clinical remission in patients who had achieved a clinical response in the induction phase. This phase enrolled 544 patients who were re-randomized 2:1 to receive mirikizumab 200 mg or placebo subcutaneously every four weeks for 40 weeks (mirikizumab: 49.9%; placebo: 25.1%; p<0.001).

All major secondary endpoints were achieved in both trials, including clinical response, endoscopic remission, and bowel urgency. Bowel urgency, in particular, was tremendously improved in patients who responded to the treatment, an important achievement because relief from this symptom is a major unmet patient need.

Mirikizumab demonstrated a favorable safety profile in both trials, with adverse events consistent with those expected in this patient population. These safety findings further support the potential of mirikizumab as a well-tolerated therapy for long-term use. The data showed not only rapid relief of symptoms but also the potential to maintain remission over the long term.