FDA approves Skyrizi for moderately to severely active Crohn's disease
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The FDA has approved AbbVie’s Skyrizi for the treatment of adults with moderately to severely active Crohn’s disease, according to a company press release.
Previously approved in the United States for the treatment of adult patients with moderately to severely active plaque psoriasis and psoriatic arthritis, Skyrizi (risankizumab-rzaa, AbbVie) is the first interleukin-23 inhibitor to enter the Crohn’s disease market.
“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,” Thomas Hudson, MD, senior vice president of research and development and chief scientific officer at AbbVie, said in the release. “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 FDA based its approval on results from two phase 3 induction trials — ADVANCE and MOTIVATE — that assessed clinical remission and endoscopic response with IV risankizumab (in 600 mg and 1,200 mg doses) vs. placebo over 12 weeks, as well as a phase 3 maintenance trial — FORTIFY — that examined the safety and efficacy of subcutaneous risankizumab (in 180 mg and 360 mg doses) vs. placebo over 52 weeks among patients who achieved clinical response during the induction studies.
According to study results from the induction trials, a significantly greater proportion of patients treated with risankizumab achieved endoscopic response and clinical remission compared with placebo as early as week 4. Additionally, in the 52-week maintenance trial, a significantly greater proportion of patients achieved the co-primary endpoints of endoscopic response and clinical remission vs. patients in the placebo group after 1 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,” Marla Dubinsky, MD, co-director of the Susan and Leonard Feinstein IBD Center at Mount Sinai, said in the release. “This approval provides health care professionals with a greatly needed additional option for treating the disruptive symptoms of Crohn's disease.”
According to the FDA, common adverse events reported by CD patients treated with risankizumab include upper respiratory infections, headache, fever, abdominal pain, back pain, joint pain and injection site reactions.
Perspective
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Considering the last treatment advance occurred 6 years ago and currently available medications have various limitations, the introduction of risankizumab-rzaa to the treatment armamentarium for moderate-to-severe Crohn’s disease has been a welcomed addition.
ADVANCE was a phase 3 induction study that enrolled both biologic-naïve and biologic-exposed patients. MOTIVATE, another phase 3 induction trial, included only biologic-exposed patients. Across both studies, 42% to 45% of participants treated with risankizumab-rzaa experienced clinical remission, but endoscopic response was only 29% in the MOTIVATE study vs. 40% in the ADVANCE trial. In the phase 3 maintenance trial, FORTIFY, which included both biologic-naïve and biologic-exposed patients, the clinical remission rate with risankizumab-rzaa was 57% and endoscopic response was 48%.
Although there is still work to be done in breaking the therapeutic ceiling with biologic therapy, these rates demonstrate that risankizumab-rzaa is a promising treatment option for CD. According to one systematic review and network meta-analysis of biologics and small molecules in luminal CD, risankizumab-rzaa 600 mg was found to be most efficacious in inducing remission in both biologic-naïve and biologic-exposed patients.
One unique aspect of risankizumab-rzaa is its selective mechanism of action. As the first specific interleukin (IL)-23 inhibitor for CD, the development of risankizumab-rzaa indicates that our understanding of the cytokine pathway and its relationship with IBD continues to evolve. I look forward to seeing the outcomes of an ongoing head-to-head study between risankizumab-rzaa and ustekinumab, an IL-12 and 23 inhibitor. In addition to potentially gaining a better understanding of medication effects on IBD pathophysiology, this study will help determine how to position risankizumab-rzaa in patients with CD.
Logistically, a higher level of care coordination is required, given that the induction doses are administered intravenously while the maintenance dose is administered subcutaneously and may be covered under separate benefits (medical vs. pharmacy). Additionally, the maintenance dose is administered via a novel device called an on-body injector, and patients will require training from staff to ensure correct use.
While we look forward to the day when we can say that the “sky is the limit” in regard to identifying a cure or developing medications that provide much higher clinical remission and endoscopic response rates, risankizumab-rzaa is presently an exciting advance for CD and offers another therapeutic option for our patients.
Reference:
Barberio B, et al. Gut. 2022;doi:10.1136/gutjnl-2022-328052.
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