FDA Approves Mirikizumab for Moderately to Severely Active Ulcerative Colitis

The FDA has approved mirikizumab-mrkz (Omvoh; Eli Lilly and Company) infusion 300 mg/15 mL and injection 100 mg/mL to treat moderately to severely active ulcerative colitis (UC) in adults. The approval makes mirikizumab the first interleukin-23p19 (IL-23p19) antagonist approved for adult patients with this condition and is the only UC treatment that selectively targets the p19 subunit of IL-23, which has been linked to UC-related inflammation, according to Eli Lilly.

"I see many people with ulcerative colitis who previously tried other biologic treatments, and they are still searching for an effective option that can offer rapid and lasting improvements," Bruce Sands, MD, MS, Dr. Burrill B. Crohn Professor of Medicine and chief of the Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, said in a press release. "[The] approval represents a novel scientific advancement, providing a treatment that may offer relief from three key symptoms—stool frequency, rectal bleeding and bowel urgency—regardless of past biologic use."

The FDA based the approval on findings from the LUCENT clinical program, which included a pair of randomized, double-blind, placebo-controlled, phase 3 trials. One of the trials was a 12-week induction study (UC-1) and the other was a 40-week maintenance study (UC-2) for 52 weeks of continuous treatment. All of the patients enrolled in the program received prior therapy—including biologics—that either didn’t work, stopped working, or were not tolerable.

Following 12 weeks of mirikizumab therapy, 65% of patients achieved clinical response and 24% achieved remission compared with 43% and 15% in the placebo cohorts, respectively. Among those who achieved clinical response at 12 weeks with mirikizumab, 51% of these patients and 45% of those who failed prior treatment with a biologic or Janus kinase inhibitor achieved clinical remission at 1 year compared with 27% and 15%, respectively, in the placebo cohort.

Among patients achieving a clinical response at 12 weeks, 50% achieved steroid-free clinical remission at 1 year vs 27% in the placebo cohort. In a post-hoc analysis, 99% of those who achieved clinical remission at 1 year were steroid-free and those in steroid-free clinical remission remained so for at least 3 months before the end of the 52-week assessment. In patients achieving clinical remission at 12 weeks, 66% maintained it through 1 year of continuous treatment vs 40% in the placebo cohort.

Symptoms such as rectal bleeding and stool frequency showed a rapid improvement as early as 3 weeks in the mirikizumab cohort.

The investigators noted that the LUCENT trials were the first to use the Urgency Numeric Rating Scale (NRS) of 0-10, a patient-centric evaluation in which zero means no bowel urgency and 10 is the worst possible bowel urgency. At baseline of the trials, investigators observed a median Urgency NRS weekly average score of 7. In those with an Urgency NRS weekly average score ≥3 at baseline and who responded to induction treatment with mirikizumab, 39% administered mirikizumab achieved a weekly average score of 0 to 1 at 1 year vs 23% in the placebo cohort.

"Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis," said Michael Osso, president and chief executive officer, Crohn's & Colitis Foundation. "[The] approval of Omvoh offers new hope for those who have tried other therapies and still find themselves making accommodations for the uncertainty of bowel urgency-related accidents and other symptoms associated with ulcerative colitis."

Patients administered mirikizumab were found to be less likely to discontinue treatment because of adverse events (AEs), which was reported in 1.6% of patients in the mirikizumab cohort in the UC-1 trial and 1.5% in the mirikizumab cohort in the UC-2 trial vs 7.2% in UC-1 and 8.3% in UC-2, respectively, in the placebo cohort. The most common AEs associated with mirikizumab reported in at least 2% of patients at a higher frequency than placebo were upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.

Mirikizumab’s labeling includes warnings and precautions for hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and immunizations. Lilly said it anticipates mirikizumab to be available in the United States in the coming weeks.

"Omvoh addresses key symptoms that matter most to patients and represents our patient-centric approach to treatment innovation," said Patrik Jonsson, Lilly executive vice president, president of Lilly Immunology and Lilly USA, and chief customer officer, in a press release. "Omvoh's approval is a significant moment for Lilly's growing Immunology portfolio, and we are excited to work with the gastroenterology community to set high expectations of care for people living with ulcerative colitis."

Reference

FDA Approves Lilly's Omvoh™ (mirikizumab-mrkz), A First-in-Class Treatment for Adults with Moderately to Severely Active Ulcerative Colitis. Eli Lilly and Company. News release. October 26, 2023. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-omvohtm-mirikizumab-mrkz-first-class