AbbVie announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended the approval of upadacitinib (Rinvoq, 45 mg [induction dose] and 15 mg and 30 mg [maintenance doses]) for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.
"The recent CHMP recommendation to approve upadacitinib for use in Crohn's disease is a momentous step, bringing us closer to offering a first-of-its-kind, once-daily oral treatment that can make a difference for people living with this disease," said Roopal Thakkar, M.D., senior vice president, development, regulatory affairs and chief medical officer, AbbVie. "We remain steadfast in our commitment to researching and developing treatment options as part of a diverse portfolio of therapies for those living with inflammatory bowel diseases."
AbbVie's application for the approval of upadacitinib in Crohn's disease is supported by data from two induction studies, U-EXCEED and U-EXCEL, and one maintenance study, U-ENDURE. Patients receiving upadacitinib were treated with 45 mg once daily for the induction studies, and were randomized to receive either 15 mg or 30 mg once-daily doses for the maintenance study. Across all three phase 3 studies, a significantly greater proportion of patients treated with upadacitinib achieved the co-primary endpoints of clinical remission per SF/AP (defined as average daily stool frequency [SF] =2.8 and abdominal pain [AP] score =1.0 and neither greater than baseline) and endoscopic response (defined as decrease in simple endoscopic score for Crohn's disease [SES-CD] >50% from baseline of the induction) compared to placebo.
In all three studies, a statistically significant greater proportion of patients treated with upadacitinib achieved the key secondary endpoint of endoscopic remission (defined as SES-CD =4 and at least a 2-point reduction vs. baseline and no subscore >1). Additionally, more upadacitinib-treated patients achieved SES-CD ulcerated surface subscore of 0 at weeks 12 and 52 (nominal p-value<0.001) in patients with SES-CD ulcerated surface subscore =1 at baseline. Absence or disappearance of ulceration coupled with improvements seen by endoscopy are associated with mucosal healing.
The safety profile of upadacitinib in Crohn's disease was generally consistent with the known safety profile of upadacitinib. Similar rates of serious adverse events including serious infections were observed between patients receiving upadacitinib and placebo. Reports of malignancy, major cardiovascular events, venous thromboembolic events and gastrointestinal perforation were infrequently observed (<1.0 Events/100 Patient-Years).
"The impact of Crohn's disease extends beyond the gut to include systemic symptoms such as fatigue, bowel symptoms and social and emotional functioning. Treatment options that achieve critical endpoints such as clinical remission and endoscopic response can make a difference in managing the challenging symptoms of this condition and health-related outcomes related to quality of life," said Jean-Fr
