AbbVie Submits Application to FDA for Risankizumab in Ulcerative Colitis

Credit: US Food and Drug Administration

AbbVie has submitted applications for a new indication to the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for risankizumab (Skyrizi) at induction and maintenance doses for the treatment of moderately to severely active ulcerative colitis.¹

The regulatory submissions for rizankizumab 1200 mg intravenous induction dose and 180 mg and 360 mg subcutaneous maintenance dose, which were announced by AbbVie on August 28, 2023, are based on data from the INSPIRE and COMMAND trials.¹

"While there has been advancement in therapies to treat ulcerative colitis, there is still an ongoing need for additional treatments to help those seeking relief from its disruptive effects," said Roopal Thakkar, MD, senior vice president of Development in Regulatory Affairs and chief medical officer at AbbVie.¹"These submissions demonstrate our continued commitment to helping people living with IBD, and we look forward to providing a potential new treatment option for the management of ulcerative colitis."

An interleukin-23 inhibitor, risankizumab is already approved by both the FDA and EMA for treatment of plaque psoriasis, psoriatic arthritis, and Crohns disease. Risankizumab had not yet been approved for ulcerative colitis, but data from the Phase 3 clinical trials INSPIRE and COMMAND support the recent FDA and EMA applications for use as an induction and maintenance treatment.¹

INSPIRE

AbbVie announced topline results of the INSPIRE trial on March 23, 2023. A multicenter, randomized, double-blind, placebo-controlled trial, INSPIRE evaluated the efficacy and safety of risankizumab 1200 mg administered every 4 weeks as induction therapy in subjects with moderately to severely active ulcerative colitis.²

With this in mind, the trial was designed with a primary endpoint of clinical remission at week 12. For the purpose of analysis, clinical remission was defined using an adapted Mayo Score, defined as a stool frequency subscore of ≤1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore ≤1 without friability.²

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<0.00001). 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).²

The March 2023 release noted no new safety risks were observed and the known safety profile remained consistent. The most common adverse events observed in the risankizumab group were COVID-19, anemia, and arthralgia.²

COMMAND

AbbVie announced risankizumab achieved positive topline results in COMMAND, its second phase 3 clinical trial, on June 15, 2023. A 52-week maintenance study of patients from INSPIRE, the trial used a rerandomized withdrawal design to evaluate the efficacy and safety of subcutaneous risankizumab 180 mg or 360 mg relative to induction therapy only.³

The trial had a primary endpoint of clinical remission. Results of the trial demonstrated 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).³

The release from AbbVie noted the trial met key secondary endpoints including endoscopic improvement, histologic endoscopic mucosal improvement, and steroid-free. The release also noted safety results remained consistent with previous trial data, with the most common adverse events observed in the risankizumab group being COVID-19, nasopharyngitis, and arthralgia.³

References

1. AbbVie. AbbVie submits regulatory applications to FDA and EMA for risankizumab (SKYRIZI®) in ulcerative colitis. News Center. August 28, 2023. Accessed August 28, 2023. https://news.abbvie.com/news/press-releases/abbvie-submits-regulatory-applications-to-fda-and-ema-for-risankizumab-skyrizi-in-ulcerative-colitis.htm?view_id=2421.
2. AbbVie. Risankizumab (SKYRIZI®) achieves primary and all secondary endpoints in phase 3 induction study in patients with ulcerative colitis. News Center. March 23, 2023. Accessed August 28, 2023. https://news.abbvie.com/news/press-releases/risankizumab-skyrizi-achieves-primary-and-all-secondary-endpoints-in-phase-3-induction-study-in-patients-with-ulcerative-colitis.htm.
3. AbbVie. Risankizumab (SKYRIZI®) met primary and key secondary endpoints in 52-week phase 3 maintenance study in ulcerative colitis patients. News Center. June 15, 2023. Accessed August 28, 2023. https://news.abbvie.com/news/press-releases/risankizumab-skyrizi-met-primary-and-key-secondary-endpoints-in-52-week-phase-3-maintenance-study-in-ulcerative-colitis-patients.htm.