Mirikizumab rebounds to win FDA approval as first IL-23p19 agonist for ulcerative colitis
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The FDA has approved Eli Lilly’s Omvoh infusion/injection as the “first and only” interleukin-23p19 antagonist for the treatment of patients with moderately to severely active ulcerative colitis, according to a company release.
The agency had denied Eli Lilly’s biologic license application for Omvoh (mirikizumab-mrkz) for this indication earlier this year, citing only concerns over the proposed manufacturing of the drug rather than the clinical data package, safety or label.
“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 at the Icahn School of Medicine at Mount Sinai, said in the release. “[This] 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 its decision on data from the LUCENT program, which included two randomized double-blind, placebo-controlled phase 3 trials assessing the efficacy and safety of Omvoh in adults with moderately to severely active UC. Patients included in the trials were either biologic-naïve or biologic-refractory who had previously failed at least one biologic. The UC-1 trial was a 12-week induction study (n=1,279) and UC-2 (n=581) was a 40-week maintenance study, for a total of 52 weeks of continuous treatment.
The primary endpoint for the program was clinical remission at week 12 and 52. Secondary endpoints for the UC-1 trial included clinical response, endoscopic improvement and histologic-endoscopic mucosal improvement (HEMI) at week 12; secondary endpoints for the UC-2 trial included endoscopic improvement, maintenance of clinical remission in patients who achieved clinical remission at week 12, corticosteroid-free clinical remission, HEMI and bowel urgency improvement at 40 weeks.
In the UC-1 trial, patients were randomly assigned 3:1 to receive either IV Omvoh 300 mg or IV placebo every 4 weeks for 12 weeks, the release stated. Following this, patients that received Omvoh and achieved clinical response at week 12 were randomly assigned 2:1 to receive either subcutaneous injection of Omvoh 200 mg or subcutaneous placebo injection every 4 weeks for an additional 40 weeks in UC-2 trial.
At week 12, nearly two-thirds of patients (65%) who received Omvoh achieved clinical response compared with 43% of those in the placebo group, the release stated; additionally, nearly one-fourth (24%) of patients achieved clinical remission with Omvoh compared with placebo. More patients who received Omvoh attained endoscopic improvement (34% vs. 21%) and HEMI (25% vs. 14%) at week 12 compared with placebo.
According to the release, after 52 weeks, 66% of patients who achieved clinical remission with Omvoh at week 12 maintained clinical remission compared with 40% of the placebo group. Results from a post-hoc analysis showed 99% of patients who achieved clinical remission after 52 weeks were steroid-free.
Additionally, 50% of patients receiving Omvoh achieved corticosteroid-free clinical remission compared with 27% who received placebo. More patients in the Omvoh group compared with placebo achieved endoscopic improvement (58% vs. 30%) and HEMI (43% vs. 22%) at 52 weeks.
As early as 3 weeks, patients who received Omvoh saw quick improvements in rectal bleeding and stool frequency, according to the release.
The median bowel urgency (defined by Numeric Rating Scale of 0 to 10) weekly average score was 7 at baseline. Among patients who exhibited an urgency NRS weekly average score 3 and responded to induction of Omvoh, a significantly greater proportion of patients achieved a weekly average score of 0 to 1 at 52 weeks (39% vs. 23%) with Omvoh compared with placebo.
“Bowel urgency is one of the most disruptive symptoms for patients with ulcerative colitis,” Michael Osso, president and chief executive officer, Crohn's & Colitis Foundation, said in the release. “[This] 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.”
According to the release, patients who received Omvoh compared with placebo were less likely to discontinue treatment. The most common adverse reactions associated with Omvoh included upper respiratory infections, injection site reactions, arthralgia, rash, headache and herpes viral infection. The drug’s labeling also includes warnings and precautions for hypersensitivity reactions, risk of infection, tuberculosis, hepatotoxicity and immunizations.
The company noted that Omvoh will be available in the United States within the coming weeks. The drug has also been approved in the EU and Japan and the company expects more regulatory decisions worldwide in the months to follow.
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