FDA Approves Mirikizumab (Omvoh) for Ulcerative Colitis

Credit: US Food and Drug Administration

The US Food and Drug Administration has approved mirikizumab-mrkz (Omvoh) for the treatment of moderately to severely active ulcerative colitis in adults, according to a statement from Eli Lilly and Company.

Announced on October 26, 2023, the approval, which makes mirikizumab infusion (300 mg of 15 mL) and injection (100 mg of mL) the first and only IL-23p19 antagonist to receive such an indication, is based on data from a pair of phase 3 trials within the LUCENT program.

"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.¹ "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."

The initial Biologics License Application from Eli Lilly and Company for mirikizumab dates back to Q1 of 2022. The road to approval was delayed by a Complete Response Letter from the FDA in April 2023, which expressed concerns related to the proposed manufacturing of the agent. In a statement released at the time, the company noted it was working with the FDA and hoped to launch mirikizumab in the US as soon as possible.²

The approval of mirikizumab was based on the LUCENT program, which included a pair of trials named UC-1 and UC-2. The UC-1 trial was designed as a 12-week induction study and UC-2 was designed as a 40-week maintenance study. Of note, all patients in the LUCENT program had past treatments, including biologic treatments, that did not work, stopped working or that they could not tolerate.¹

In UC-1, patients were randomized 3:1 to receive mirikizumab 300 mg intravenously or placebo every 4 weeks for 12 weeks. Patients from UC-1 who achieved clinical response at week 12 with mirikizumab were randomized in a 2:1 ratio to receive mirikizumab 200 mg subcutaneous injection or placebo subcutaneous injection every 4 weeks for another 40 weeks in UC-2.

In their release, Eli Lilly and Company highlighted the following results with mirikizumab in UC-1:¹

• 24% achieved clinical remission compared to 15% of placebo (n=191 of 795 vs, n=39 of 267)
• 65% achieved a clinical response compared to 43% of placebo (n=514 of 795 vs, n=116 of 267)
• 34% achieved endoscopic improvement compared to 21% of placebo (n=274 of 795 vs, n=56 of 267)
• 25% achieved histologic-endoscopic mucosal improvement compared to 14% of placebo (n=200 of 795 vs n=38 of 267)

The following results were highlighted from UC-2:¹

• 51% achieved clinical remission compared to 27% of placebo (n=171 of 337 vs n=45 of 169)
• 99% (n=169 of 171) of patients who achieved clinical remission at one year of treatment were steroid-free for at least the previous 12 weeks.
• 50% achieved corticosteroid-free clinical remission compared to 27% of placebo (n=169 of 337 vs n=45 of 169). Patients in steroid-free remission stopped using corticosteroids for at least the previous 12 weeks prior to the one-year assessment.
• 58% achieved endoscopic improvement compared to 30% of placebo (n=195 of 337 vs n=50 of 169)
• 66% achieved maintenance of clinical remission in patients who achieved clinical remission at Week 12 compared to 40% of placebo (n=84 of 128 vs n=25 of 62)
• 43% achieved histologic-endoscopic mucosal improvement compared to 22% of placebo (n=145 of 337 vs n=37 of 169)

Bowel urgency was also assessed as an endpoint of interest in both UC-1 and UC-2. Analysis of this endpoint among responders to induction therapy in UC-1 suggested a significantly greater proportion of subjects treated with mirikizumab achieved an Urgency Numeric Rating Scale weekly average score of 0 to 1 (39% [n=119 of 307] versus 23% [n=37 of 160]) at Week 40 in UC-2.¹

Although the statement noted patients receiving were less likely to discontinue treatment due to adverse events in both UC-1 and UC-2, it highlighted upper respiratory infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection were the most common adverse reactions from mirikizumab use.¹

"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.¹ "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."

The labeling for mirikizumab contains warnings and reactions related to hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity and immunizations. According to the statement from Eli Lilly and Company, mirikizumab will be available in the US in the coming weeks.¹

"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.¹ "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."

References:

1. Eli Lilly and Company. FDA approves Lilly’s omvohTM (mirikizumab-mrkz), a first-in-class treatment for adults with moderately to severely active ulcerative colitis. Eli Lilly and Company. October 26, 2023. Accessed October 26, 2023. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-omvohtm-mirikizumab-mrkz-first-class.
2. Eli Lilly and Company. U.S. Food and Drug Administration Issues Complete Response Letter for mirikizumab. Eli Lilly and Company. April 13, 2023. Accessed October 26, 2023. https://investor.lilly.com/news-releases/news-release-details/us-food-and-drug-administration-issues-complete-response-1.