• 22 Jun 2022
• Admin
• News Article

US FDA approves AbbVies interleukin-23 inhibitor Skyrizi to treat moderately to severely active Crohns disease

AbbVie announced that the US Food and Drug Administration (FDA) has approved Skyrizi (risankizumab-rzaa) as the first and only specific interleukin-23 (IL-23) inhibitor for the treatment of adults with moderately to severely active Crohn's disease (CD). In two induction and one maintenance clinical trials, Skyrizi demonstrated significant improvements in endoscopic response (defined as a decrease of greater than 50% from the baseline Simple Endoscopic Score in CD [SES-CD] or for patients with isolated ileal disease and SES-CD of 4, at least a 2-point reduction from baseline) and clinical remission (defined as a Crohn's Disease Activity Index [CDAI] of less than 150), compared to placebo, as both an induction and maintenance therapy. "We are proud to offer the first new treatment option in six years for moderately to severely active CD, which may provide patients with a meaningful level of endoscopic improvement," said Thomas Hudson, M.D., 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." The dosing regimen for Skyrizi for the treatment of CD is 600 mg administered by intravenous infusion over at least one hour at week 0, week 4, and week 8, followed by 360 mg self-administered by subcutaneous injection (SC) with an on-body injector (OBI) at week 12, and every 8 weeks thereafter. A 180 mg self-administered SC maintenance dose option remains under review by the FDA. The co-primary endpoints of the clinical trials were endoscopic response and clinical remission. In the 12-week induction studies, ADVANCE and MOTIVATE, a significantly greater proportion of patients treated with Skyrizi achieved endoscopic response and clinical remission compared to placebo. As early as week 4, clinical response (defined as a 100-point reduction in CDAI) and clinical remission were achieved in a significantly greater proportion of patients receiving Skyrizi as compared to placebo. In the 52-week maintenance trial, FORTIFY, a significantly greater proportion of patients achieved the co-primary endpoints of endoscopic response and clinical remission as compared with the placebo group (risankizumab induction responders) after one year. "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, M.D., chief, division of pediatric gastroenterology for the Mount Sinai Health System, co-director of the Susan and Leonard Feinstein IBD Center at Mount Sinai. "This approval provides healthcare professionals with a greatly needed additional option for treating the disruptive symptoms of Crohn's disease." Skyrizi may cause serious side effects, including: Serious allergic reactions: Stop using Skyrizi and get emergency medical help right away if you get any symptoms of a serious allergic reaction. Infections: Skyrizi may increase your risk of infections. Before starting treatment, your doctor should check you for infections and tuberculosis. Tell your doctor right away if you have an infection or symptoms of one. Skyrizi is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization of Skyrizi globally. AbbVie is committed to helping people access Skyrizi and other medicines, including offering a patient support program and co-pay card that may reduce out-of-pocket costs to as little as $5 per month for eligible, commercially-insured patients, who may also be reimbursed for out-of-pocket costs related to IV administration. For those with limited or no health insurance, AbbVie offers myAbbVie Assist, a patient assistance program that provides Skyrizi at no charge to those who qualify. Crohn's disease is a chronic, systemic disease that manifests as inflammation within the gastrointestinal (or digestive) tract, causing persistent diarrhea and abdominal pain. It is a progressive disease, meaning it gets worse over time, and in many cases leads to surgery. Because the signs and symptoms of Crohn's disease are unpredictable, it causes a significant burden on people living with the disease. The ADVANCE and MOTIVATE studies are phase 3, multicenter, randomized, double-blind, placebo-controlled induction studies designed to evaluate the efficacy and safety of two doses of risankizumab, 600 mg and 1200 mg, in adults with moderately to severely active Crohn's disease, compared to placebo. Both studies included different sets of primary and secondary endpoints for outside US (OUS) protocol and US protocol. The primary endpoints were achievement of clinical remission (per PRO-2 for the OUS protocol, which was measured by daily stool frequency and abdominal pain score, and per CDAI for the US protocol, which was measured by a CDAI score less than 150) and endoscopic response (for both protocols) at week 12. Endoscopic response is defined as a decrease of greater than 50% from the baseline SES-CD or for patients with isolated ileal disease and SES-CD of 4, at least a 2-point reduction from baseline, as scored by a central reviewer. The ADVANCE study included a mixed population of patients who had responded inadequately or were intolerant to conventional and/or biologic therapy. The MOTIVATE study evaluated patients who had responded inadequately or were intolerant to biologic therapy. Topline results of the studies were shared in January 2021.