FDA Approves Risankizumab (Skyrizi) for Ulcerative Colitis

AbbVie has announced the US Food and Drug Administration (FDA) has approved risankizumab-rzaa (Skyrizi) for adults with moderately to severely active ulcerative colitis (UC), making it the first interleukin (IL)-23 specific inhibitor approved for both moderate to severe UC and moderate to severe Crohn disease (CD).¹

The decision is supported by data from a pair of phase 3 clinical trials showing that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, a key secondary endpoint.¹

"When treating patients with ulcerative colitis, it's important to prioritize both early and sustained clinical remission as well as endoscopic improvement," Edward V Loftus Jr, MD, Maxine and Jack Zarrow Family Professor of Gastroenterology in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, said in a press release.¹ "This approval for SKYRIZI is an important step toward addressing these treatment goals."

According to the June 18, 2024 press release, dosing of risankizumab-rzaa for this indication includes a 12-week induction period with 3 1200 mg doses delivered every 4 weeks, followed by maintenance therapy of either 180 mg or 360 mg delivered every 8 weeks. Following the induction period, risankizumab-rzaa treatment can be maintained at home using a hands-free on-body injector device that takes about 5 minutes to deliver the medication following preparation steps.¹

An IL-23 inhibitor that selectively blocks IL-23 by binding to its p19 subunit, risankizumab is now approved for 4 indications across immune-mediated inflammatory diseases, including plaque psoriasis, psoriatic arthritis, CD, and most recently, UC, with approval supported by a pair of phase 3 studies, INSPIRE and COMMAND.^2,3,4

A multicenter, randomized, double-blind, placebo-controlled phase 3 study, INSPIRE evaluated the efficacy and safety of risankizumab 1200 mg IV administered every 4 weeks as induction therapy in subjects with moderately to severely active UC. The primary endpoint was clinical remission (per Adapted Mayo Score, defined as stool frequency subscore [SFS] ≤1 and not greater than baseline, rectal bleeding subscore [RBS] of 0 and endoscopic subscore ≤1 without friability) at week 12. Secondary endpoints included clinical response (decrease from baseline in the Adapted Mayo Score ≥2 points and ≥30% from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1), endoscopic improvement (endoscopic subscore ≤1 without friability), and histologic and endoscopic mucosal improvement (HEMI) (endoscopic subscore of 0 or 1 without friability and Geboes score ≤3.1) at week 12.¹

Results of the trial suggested clinical remission was achieved in 20.3% of patients randomized to risankizumab remission compared to 6.2% of patients receiving placebo (P <.00001). Analysis of secondary endpoints indicated a significantly greater proportion of patients treated with risankizumab achieved endoscopic improvement at week 12 compared to placebo (36.5% vs 12.1%; P <.00001). Additionally, more patients treated with risankizumab achieved histologic-endoscopic mucosal improvement at week 12 than those receiving placebo (24.5% vs 7.7%, P <.00001).⁵

A phase 3, multicenter, randomized, double-blind, controlled, 52-week maintenance study, COMMAND evaluated the efficacy and safety of risankizumab 180 mg or 360 mg SC in adults with moderately to severely active UC. The study followed a re-randomized withdrawal design in which all patients received risankizumab IV induction and those who responded to risankizumab were re-randomized to receive risankizumab 180 mg or 360 mg SC or withdrawal from risankizumab treatment (induction-only control group). For those randomized to withdraw from risankizumab treatment, the rest of the study duration was a risankizumab washout. The objective of the study was to evaluate the efficacy and safety of risankizumab 180 mg or 360 mg as maintenance therapy versus withdrawal from risankizumab treatment (control) in patients with moderately to severely active ulcerative colitis who responded to risankizumab IV induction in the INSPIRE study.¹

The primary endpoint was clinical remission (per Adapted Mayo Score, defined as SFS ≤1 and not greater than baseline, RBS of 0 and endoscopic subscore ≤1 without evidence of friability) at week 52. Secondary endpoints included endoscopic improvement (endoscopic subscore ≤1 without evidence of friability), histologic and endoscopic mucosal improvement (HEMI) (endoscopic subscore of ≤1 without evidence of friability and Geboes score ≤3.1), and steroid-free clinical remission (defined as clinical remission per Adapted Mayo Score at week 52 and corticosteroid free for ≥90 days prior to week 52) at week 52.¹

Results showed a greater number of patients who received risankizumab 180 mg or 360 mg achieved clinical remission at week 52 (40% and 38%, respectively) compared to the induction-only control group (25%; P < .01). Of note, the trial also met key secondary endpoints including endoscopic improvement, histologic endoscopic mucosal improvement, and steroid-free remission.⁵

"Today's approval of SKYRIZI for ulcerative colitis expands our IBD portfolio and demonstrates our commitment to helping address ongoing needs of patients," said Roopal Thakkar, MD, senior vice president, chief medical officer, global therapeutics, AbbVie.¹ "We will continue to invest in transforming the treatment landscape and the lives of people suffering from lBD."

References:

1. ^{U.S. FDA Approves SKYRIZI® (risankizumab-rzaa) for Ulcerative Colitis, Expanding AbbVie's Portfolio Across Inflammatory Bowel Disease. June 18, 2024. Accessed June 18, 2024. https://www.prnewswire.com/news-releases/us-fda-approves-skyrizi-risankizumab-rzaa-for-ulcerative-colitis-expanding-abbvies-portfolio-across-inflammatory-bowel-disease-302176163.html}
2. ^{Gingerich C. FDA Approves Risankizumab for Plaque Psoriasis. HCPLive. April 24, 2019. Accessed June 18, 2024. https://www.hcplive.com/view/fda-approves-risankizumab-for-plaque-psoriasis}
3. ^{HCPLive. Risankizumab Receives FDA Approval for Active Psoriatic Arthritis. January 24, 2022. Accessed June 18, 2024. https://www.hcplive.com/view/risanikizumab-receives-fda-approval-for-active-psoriatric-arthritis}
4. ^{Walter, K. FDA Approves Risankizumab For Crohn’s Disease. June 17, 2022. Accessed June 18, 2024. https://www.hcplive.com/view/fda-appropves-risankizumab-crohns-disease}
5. ^{Brooks, A. AbbVie Submits Application to FDA for Risankizumab in Ulcerative Colitis. HCPLive. August 28, 2023. Accessed June 18, 2024. https://www.hcplive.com/view/abbvie-submits-application-to-fda-for-risankizumab-in-ulcerative-colitis}