Eli Lilly and Company announced today that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted a marketing authorization (MA) for mirikizumab (OMVOH®) for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, have lost response or are intolerant to conventional therapy or biologic treatment.
“Ulcerative colitis is a chronic, relapsing inflammatory disease affecting the colon. It is characterized by symptoms of diarrhea, bleeding and urgency, with multidimensional and often negative effects on patients’ personal, psychological, professional and social well-being. Our understanding of etiopathogenesis is improving but our treatment options remain limited,” said Professor Jimmy Limdy, Consultant Gastroenterologist/Head of IBD Section at Northern Care Alliance NHS Foundation Trust and Professor of Gastroenterology at the University of Manchester. “The recent approval of Mirikizumab, the first IL-23p19 inhibitor, is positive news for eligible people living with ulcerative colitis and the gastroenterologists/specialists who care for them. This is a significant scientific advance welcomed by the medical community.
Sarah Sleight, chief executive of Crohn’s & Colitis UK, welcomed the news: “Over 500,000 people in the UK are living with Crohn’s disease and ulcerative colitis. They are lifelong conditions for which there is no known cure, and the symptoms are painful and debilitating. Existing medications may not work for some people or even stop working for others. Expanding treatment options for eligible people living with colitis is a promising step forward and we welcome the MHRA’s decision to authorize mirikizumab.
This authorization establishes Mirikizumab as the first IL-23p19 antagonist to be authorized in the UK for the treatment of adults with moderate to severe ulcerative colitis and reflects our commitment to immunological diseases with high unmet need. We understand how important it is to have new treatment options for eligible patients, and Lilly would like to thank the patients and researchers around the world who have made this possible.”
Laura Steele, President and General Manager, Northern Europe, Eli Lilly and Company
The approval was based on results from the LUCENT program, which included two randomized, double-blind, placebo-controlled phase 3 clinical trials consisting of one 12-week induction study (LUCENT-1) and one 40-week maintenance study (LUCENT – 2) for 52 weeks of continuous treatment.
In the LUCENT-1 induction study, 1162 patients were enrolled in the primary efficacy population. Patients were randomized 3:1 to receive mirikizumab (300 mg) intravenously (IV) or placebo IV every 4 weeks for 12 weeks. After 12 weeks of treatment with mirikizumab, 24.2% (n=210/868) of patients achieved the primary endpoint of clinical remission compared with 13.3% (n=39/294) on placebo.
544 patients who achieved a clinical response to mirikizumab in LUCENT-1 (63.5%, n=551/868) were re-randomized 2:1 to receive a subcutaneous injection of mirikizumab (200 mg) or a subcutaneous injection of placebo each 4 weeks for another 40 weeks in LUCENT-2. Of LUCENT-1 patients who achieved a clinical response at week 12, 49.9% (n=182/365) achieved clinical remission (primary endpoint) and 43.3% (n=158/365) achieved histological-endoscopic mucosal remission (secondary endpoint) at one year, compared to placebo (25.1%, n=45/179 and 21.8%, n=39/179 for clinical remission and histological-endoscopic remission, respectively mucosal remission).
Mirikizumab-treated patients achieved greater reductions in rectal bleeding and bowel frequency after just two weeks. The LUCENT studies also examined endpoints such as bowel urgency remission and bowel urgency severity using the validated Numerical Urgency Rating Scale (NRS) of 0-10, with zero indicating no urgency and 10 being the most the bad possible urgency. A reduction in the severity of the urge to defecate was observed as early as two weeks in patients treated with mirikizumab. After treatment with mirikizumab, 42.9% (n=144/336) of patients achieved remission of bowel urgency at one year, compared with 25% (n=43/172) on placebo.
The phase 3 LUCENT clinical program also evaluated the safety profile of mirikizumab. The most commonly reported adverse reactions were upper respiratory tract infections (7.9%, most commonly nasopharyngitis), headache (3.3%), rash (1.1%), and injection site reactions (8.7%). , subcutaneous injection, LUCENT-2).
Adverse reactions from clinical trials (Table 1) are listed by MedDRA system organ class. The frequency category for each reaction is based on the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000).