AbbVie has submitted an application to the Food and Drug Administration (FDA) for a new indication for upadacitinib in the treatment of adults with moderately to severely active Crohn disease.

The application is supported by data from the 2 randomized, double-blind, placebo-controlled phase 3 induction studies, U-EXCEED (ClinicalTrials.gov Identifier: NCT03345836) and U-EXCEL (ClinicalTrials.gov Identifier: NCT03345849), and one phase 3 maintenance study, U-ENDURE (ClinicalTrials.gov Identifier: NCT03345823).

The studies evaluated the efficacy and safety of upadacitinib in adults with moderately to severely active Crohn disease who had an inadequate response to or were intolerant of biologic therapy. In the induction studies, patients were randomly assigned to receive upadacitinib 45mg or placebo once daily for 12 weeks. In the maintenance study, patients were re-randomized to receive upadacitinib 15mg, 30mg, or placebo once daily for up to 52 weeks. 

Findings from all studies showed that a greater proportion of patients treated with upadacitinib achieved clinical remission (measured by the Crohn Disease Activity Index [CDAI] or by patient-reported symptoms of stool frequency/abdominal pain [SF/AP]) and endoscopic response compared with those who received placebo (coprimary endpoints):

  • U-EXCEED Induction: Clinical remission per CDAI: 39% vs 21% at week 12 (P <.0001); Clinical remission per SF/AP: 40% vs 14% at week 12 (P <.0001); Endoscopic response: 35% vs 4% at week 12 (P <.0001).
  • U-EXCEL Induction: Clinical remission per CDAI: 49% vs 29% at week 12 (P <.0001); Clinical remission per SF/AP: 51% vs 22% at week 12 (P <.0001); Endoscopic response: 46% vs 13% at week 12 (P <.0001).
  • U-ENDURE Maintenance for upadacitinib 15mg and 30mg: Clinical remission per CDAI: 37% and 48% vs 15% at week 52 (P <.0001); Clinical remission per SF/AP: 36% and 46% vs 14% at week 52 (P <.0001); Endoscopic response: 28% and 40% vs 7% at week 52 (P <.0001).

Findings from the maintenance study also showed that 19% and 29% of patients receiving upadacitinib 15mg and 30mg, respectively, achieved endoscopic remission compared with 5% of the placebo group. Among patients taking corticosteroids at baseline, a significantly higher proportion of patients treated with upadacitinib 15mg or 30mg achieved corticosteroid-free clinical remission per CDAI and per SF/AP compared with placebo at week 52.

The safety profile of upadacitinib was consistent with that seen in previous studies across indications. There were no new safety risks identified. Adverse reactions reported during induction or maintenance included nasopharyngitis, acne, infections and anemia.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is marketed under the trade name Rinvoq and is currently approved for the treatment of ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and atopic dermatitis.

References

  1. AbbVie submits regulatory applications to FDA and EMA for upadacitinib (Rinvoq®) in Crohn’s disease. News release. AbbVie. Accessed July 27, 2022. https://www.prnewswire.com/news-releases/abbvie-submits-regulatory-applications-to-fda-and-ema-for-upadacitinib-rinvoq-in-crohns-disease-301593950.html
  2. Upadacitinib (Rinvoq®) achieved primary and key secondary endpoints in first phase 3 induction study in patients with Crohn’s disease. News release. AbbVie. December 6, 2021. Accessed July 27, 2022. https://news.abbvie.com/news/press-releases/upadacitinib-rinvoq-achieved-primary-and-key-secondary-endpoints-in-first-phase-3-induction-study-in-patients-with-crohns-disease.htm
  3. Second phase 3 induction study confirms upadacitinib (Rinvoq®) improved clinical and endoscopic outcomes in patients with Crohn’s disease. News release. AbbVie. February 24, 2022. Accessed July 27, 2022. https://news.abbvie.com/news/press-releases/news-type/rd-news/second-phase-3-induction-study-confirms-upadacitinib-rinvoq-improved-clinical-and-endoscopic-outcomes-in-patients-with-crohns-disease.htm
  4. Upadacitinib (Rinvoq®) achieved clinical remission and endoscopic response at one year in phase 3 maintenance study in patients with Crohn’s disease. News release. AbbVie. May 11, 2022. Accessed July 27, 2022. https://news.abbvie.com/news/press-releases/upadacitinib-rinvoq-achieved-clinical-remission-and-endoscopic-response-at-one-year-in-phase-3-maintenance-study-in-patients-with-crohns-disease.htm