Mirikizumab shows efficacy in moderate-to-severe UC

William J. Sandborn

WASHINGTON — Mirikizumab, an anti-interleukin-23 therapy developed by Eli Lilly, showed efficacy in treating patients with moderate-to-severe ulcerative colitis, according to research presented at Digestive Disease Week.

Perspective from Stephen B. Hanauer, MD

William J. Sandborn, MD, of the University of California San Diego, said this was the first study of an IL-23 monoclonal antibody in patients with UC.

“The pro-inflammatory cytokine interleukin-23 plays a critical role in the pathogenesis of inflammatory bowel disease,” Sandborn said in a presentation. “The blockade of the IL-23 pathway has previously demonstrated efficacy in Crohn’s disease.”

For the phase 2 trial, the researchers randomly placed patients who had failed at least one conventional therapy for UC into four groups; placebo (n = 63), mirikizumab 50 mg (n = 63), mirikizumab 200 mg (n = 62) with the possibility of exposure-based increases, or a fixed mirikizumab dose of 600 mg (n = 61). The investigators then compared the groups for rates of clinical remission, clinical response, endoscopic healing, endoscopic remission and symptomatic remission.

At week 12, Sandborn and colleagues found that patients treated with the 200 mg dose had better clinical remission rates than placebo (P < .01), while the 50 mg and 600 mg groups did not. Endoscopic healing rates were greater for both the 50 mg and 200 mg groups compared with placebo (P < .05). Clinical response was greater in all the mirikizumab groups, Sandborn said.

While symptomatic remission rates were greater in the 200 mg and 600 mg groups (P < .01), endoscopic remission rates were similar among all groups.

Sandborn said the findings show that mirikizumab was efficacious in the induction treatment for patients with moderate-to-severe UC.

“Subgroup analysis based on prior biologic therapy, demonstrates trends towards efficacy in both biologic naive and biologic experienced patients, with a relatively greater effect in biologic naive patients,” Sandborn said. – by Alex Young

Reference :

Sandborn WJ, et al. Abstract 882. Presented at: Digestive Disease Week; June 2-5, 2018; Washington, D.C.

Disclosures: Sandborn reports financial ties to Qu Biologics, Seattle Genetics, Avaxia, Celgene, Takeda, Medimmune, Arena Pharmaceuticals, Ferring Research Institute, Ambrx, Kyowa Hakko Kirin Pharma, AbbVie, Palatin, Akros Pharma, UCB Pharma, Index Pharmaceuticals, Vascular Biogenics, and Atlantic Healthcare Pharmaceuticals. Please see the DDW faculty disclosure index for a list of all other authors’ relevant financial disclosures.

Perspective

Stephen B. Hanauer, MD

Ustekinumab, approved for moderate-to-severe Crohn’s disease, targets both interleukin 12 and interleukin 23 by inhibition of the p40 subunit that is present on both IL-12 and IL-23 receptors. The recognition that IL-23, thought to be the more relevant target, has a unique p19 subunit distinct from IL-12 affords the opportunity of an even more specific therapy and avoiding any potential impact of IL-12 inhibition. Several pharmaceutical companies are in the process of developing specific IL-23 inhibition by targeting the p19 subunit, including Lilly (mirikizumab), Janssen (guselkumab), Allergan (MEDI2070) and Boehringer-Ingelheim (BI 655066) for the treatment of psoriasis and/or IBD.

In contrast to the approval of ustekinumab for Crohn’s disease (trials in ulcerative colitis are nearing completion), the positive results for mirikizumab in phase II studies in moderate-to-severe ulcerative colitis suggest that IL-23 inhibition may be another safe and effective approach in both settings of IBD.

Stephen B. Hanauer, MD

Clifford Joseph Barborka Professor of Medicine

Northwestern University Feinberg School of Medicine

Medical Director, Digestive Health Center

Disclosures: Hanauer reports financial relationships with AbbVie, Actavis, Amgen, Arena, Astellas, Boehringer-Ingelheim, Bristol-Myers Squibb, Cubist, Ferring, Genentech, Gilead, GlaxoSmithKline and Janssen.