The U.S. Food and Drug Administration (FDA) has approved mirikizumab-mrkz (Omvoh) for the treatment of moderately to severely active ulcerative colitis in adult patients. This approval, announced by Eli Lilly and Company on October 26, 2023, marks mirikizumab as the first and only interleukin-23p19 (IL-23p19) antagonist to receive this indication.
The approval is based on data derived from the LUCENT program, which includes two Phase 3 trials, UC-1 and UC-2. These trials evaluated the efficacy and safety of mirikizumab in patients with ulcerative colitis who had previously failed or were intolerant to conventional or biologic therapies.
LUCENT Program Results
The LUCENT program consisted of a 12-week induction study (UC-1) and a 40-week maintenance study (UC-2). In UC-1, patients were randomized in a 3:1 ratio to receive either mirikizumab 300 mg intravenously or placebo every four weeks for 12 weeks. Patients who achieved clinical response at week 12 with mirikizumab in UC-1 were then re-randomized in a 2:1 ratio to receive mirikizumab 200 mg subcutaneous injection or placebo subcutaneous injection every four weeks for an additional 40 weeks in UC-2.
Key findings from the UC-1 trial include:
- 24% of patients achieved clinical remission compared to 15% in the placebo group (p < 0.05).
- 65% of patients achieved a clinical response compared to 43% in the placebo group (p < 0.05).
- 34% of patients achieved endoscopic improvement compared to 21% in the placebo group (p < 0.05).
- 25% achieved histologic-endoscopic mucosal improvement compared to 14% of placebo (p < 0.05).
Key findings from the UC-2 trial include:
- 51% of patients achieved clinical remission compared to 27% in the placebo group (p < 0.05).
- 99% of patients who achieved clinical remission at one year of treatment were steroid-free for at least the previous 12 weeks.
- 50% of patients achieved corticosteroid-free clinical remission compared to 27% in the placebo group.
- 58% of patients achieved endoscopic improvement compared to 30% in the placebo group (p < 0.05).
- 66% achieved maintenance of clinical remission in patients who achieved clinical remission at Week 12 compared to 40% of placebo (p < 0.05).
- 43% achieved histologic-endoscopic mucosal improvement compared to 22% of placebo (p < 0.05).
Bowel urgency, a significant symptom for ulcerative colitis patients, was also assessed. Among responders to induction therapy in UC-1, a significantly greater proportion of subjects treated with mirikizumab achieved an Urgency Numeric Rating Scale weekly average score of 0 to 1 (39%) versus placebo (23%) at Week 40 in UC-2.
Safety Profile
While patients receiving mirikizumab were less likely to discontinue treatment due to adverse events, the most common adverse reactions included upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.
Expert Commentary
"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," said 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. "Today's 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."
Michael Osso, president and chief executive officer of the Crohn's & Colitis Foundation, added, "Today's 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."
Availability
Mirikizumab is expected to be available in the U.S. in the coming weeks. The labeling includes warnings and precautions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity, and the need to complete age-appropriate immunizations according to current immunization guidelines.
