AbbVie has submitted regulatory applications to the Food and Drug Administration (FDA) for maintenance (15mg and 30mg) and induction (45mg) doses of upadacitinib for the treatment of adults with moderately to severely active ulcerative colitis.
The applications are supported by data from two phase 3 induction studies, U-ACHIEVE (ClinicalTrials.gov Identifier: NCT02819635) and U-ACCOMPLISH (ClinicalTrials.gov Identifier: NCT03653026), and 1 maintenance study, U-ACHIEVE. The studies evaluated the efficacy and safety of upadacitinib in adults with moderately to severely active ulcerative colitis. In the induction studies, patients were randomly assigned to receive either upadacitinib 45mg or placebo once daily. In the maintenance study, patients were randomly assigned to receive either upadacitinib 15mg, 30mg, or placebo once daily.
Findings from all studies showed that a greater proportion of patients treated with upadacitinib met the primary endpoint achieving the following clinical remissions compared with those treated with placebo, respectively:
- U-ACHIEVE Induction: 26% vs 5% at week 8 (P <.001)
- U-ACHIEVE Maintenance: 42% (15mg) and 52% (30mg) vs 12% at week 52 (P <.001)
- U-ACCOMPLISH Induction: 33% vs 4% at week 8 (P <.001)
Additionally, the studies met all ranked secondary endpoints including clinical response per Adapted Mayo Score, endoscopic improvement (defined as endoscopic subscore of 1 or less), and histologic-endoscopic mucosal improvement (defined as an endoscopic subscore of 1 or less and Geboes score of 3.1 or less).
The safety profile of upadacitinib was consistent with that seen in previous studies across indications. There were no new safety risks identified.
“Upadacitinib has the potential to be an important new treatment option for people with ulcerative colitis, who want to address these challenging and disruptive symptoms. We look forward to working with regulatory authorities and hope to bring upadacitinib to people with ulcerative colitis as quickly as possible,” said Tom Hudson, senior vice president of research and development, and chief scientific officer of AbbVie.
Upadacitinib, a selective and reversible Janus kinase inhibitor, is marketed under the trade name Rinvoq and is currently approved for the treatment of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to methotrexate.
In September 2021, the FDA issued a safety communication requiring revisions to the Boxed Warning for Xeljanz (tofacitinib), Xeljanz XR (tofacitinib extended-release), Olumiant (baricitinib), and Rinvoq (upadacitinib) to include information about the risks of serious cardiovascular-related events, malignancy, thrombosis, and death.
- AbbVie submits regulatory applications to FDA and EMA for upadacitinib (Rinvoq®) for the treatment of adults with moderately to severely active ulcerative colitis. News release. AbbVie. Accessed September 16, 2021. https://www.prnewswire.com/news-releases/abbvie-submits-regulatory-applications-to-fda-and-ema-for-upadacitinib-rinvoq-for-the-treatment-of-adults-with-moderately-to-severely-active-ulcerative-colitis-301378586.html.
- Upadacitinib (Rinvoq®) met the primary and all secondary endpoints in the 52-week phase 3 maintenance study in ulcerative colitis patients. News release. AbbVie. February 22, 2021. Accessed September 16, 2021. https://www.prnewswire.com/news-releases/second-phase-3-induction-study-confirms-upadacitinib-rinvoq-improved-clinical-endoscopic-and-histologic-outcomes-in-ulcerative-colitis-patients-301231986.html.
- Upadacitinib (Rinvoq™) meets primary and all ranked secondary endpoints in first phase 3 induction study in ulcerative colitis. News release. AbbVie. December 9, 2020. Accessed September 16, 2021. https://news.abbvie.com/news/press-releases/upadacitinib-rinvoq-meets-primary-and-all-ranked-secondary-endpoints-in-first-phase-3-induction-study-in-ulcerative-colitis.htm.