FDA Approves Risankizumab-rzaa for Moderately to Severely Active Crohn Disease

The FDA has approved risankizumab-rzaa (Skyrizi) for the treatment of adults with moderately to severely active Crohn disease (CD). The approval makes risankizumab-rzaa the first and only specific interleukin-23 (IL-23) inhibitor for this indication.

"We are proud to offer the first new treatment option in 6 years for moderately to severely active CD, which may provide patients with a meaningful level of endoscopic improvement," said Thomas Hudson, MD, senior vice president, research and development, chief scientific officer, AbbVie. "With more than 30 ongoing or planned trials in inflammatory bowel disease, AbbVie is committed to advancing the standards of care for patients by exploring and investing in research for those living with immune-mediated, gastroenterological conditions."

Risankizumab-rzaa is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds to the p19 subunit of the IL-23 cytokine and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses.

In a pair of induction trials, ADVANCE and MOTIVATE, and a maintenance trial called FORTIFY, risankizumab-rzaa produced significant improvements in endoscopic response, defined as a reduction of greater than 50% from the baseline Simple Endoscopic Score in CD (SES-CD) or patients with isolated ileal disease and SES-CD of 4, at least a 2-point decrease from baseline and clinical remission, defined as a CD Activity Index (CDAI) of less than 150, compared to placebo.

In the 12-week induction studies, ADVANCE and MOTIVATE, the primary endpoints were endoscopic response and clinical remission, The study showed that a significantly greater proportion of patients administered risankizumab-rzaa experienced an endoscopic response and clinical remission versus placebo. As early as week 4, clinical response and remission were observed in a significantly greater proportion of patients administered risankizumab-rzaa versus placebo.

In the FORTIFY trial, a significantly greater proportion of patients achieved the co-primary endpoints of endoscopic response and clinical remission versus the placebo cohort (risankizumab induction responders) after 1 year.

Dosing for risankizumab-rzaa is 600 mg administered by intravenous infusion over at least one hour at week 0, week 4, and week 8. This is followed by 360 mg self-administered by subcutaneous injection with an on-body injector at week 12, and every 8 weeks thereafter. The FDA is currently reviewing the 180 mg self-administered subcutaneous maintenance dose option.

"In both the induction and maintenance clinical trials, a significantly greater number of adult patients saw few or no symptoms and a meaningful reduction of visible signs of intestinal inflammation, compared to placebo," said Marla Dubinsky, MD, chief, division of pediatric gastroenterology for the Mount Sinai Health System, co-director of the Susan and Leonard Feinstein IBD Center at Mount Sinai, in a press release. "This approval provides healthcare professionals with a greatly needed additional option for treating the disruptive symptoms of Crohn's disease."

Reference

SKYRIZI® (risankizumab-rzaa) Receives FDA Approval as the First and Only Specific Interleukin-23 (IL-23) to Treat Moderately to Severely Active Crohn's Disease in Adults. AbbVie. News release. June 17, 2022. https://news.abbvie.com/news/press-releases/skyrizi-risankizumab-rzaa-receives-fda-approval-as-first-and-only-specific-interleukin-23-il-23-to-treat-moderately-to-severely-active-crohns-disease-in-adults.htm