FDA Approves Updated Indications for Upatinib/Ref in IBD Patients

The FDA approved a supplemental New Drug Application that updates the indication statement for upadacitinib for the treatment of adults with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). This updated indication now allows the use of upadacitinib before the use of a tumor necrosis factor (TNF) blocker in patients for whom these treatments are clinically undesirable and who have received at least 1 approved systemic therapy.

Upadatinib is aJanus kinase (JAK) inhibitor that has been approved to treat several immune-mediated inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and Crohn's disease, the most common form of inflammatory bowel disease (IBD). In human leukocyte assays, upadatinib more effectively inhibited cytokine-induced STAT phosphorylation mediated by JAK1 and JAK1/JAK3 compared with JAK2/JAK2-mediated STAT phosphorylation. Upadatinib was initially approved for colitis in March 2022 and for Crohn's disease in May 2023. Both approvals are initially for use in patients with moderately to severely active disease who have had an inadequate response to or are intolerant to 1 or more TNF blockers.

IBD is characterized by chronic inflammation of the gastrointestinal tract because the immune system targets the mucosa, or lining, of the intestine. Crohn's disease most commonly manifests as inflammation between the small intestine and colon, while ulcerative colitis affects the large intestine. Both diseases are progressive, meaning they worsen over time and can lead to life-threatening complications or surgery. The signs and symptoms of IBD are unpredictable and place a physical and emotional burden on patients.

The preliminary approval in ulcerative colitis is based on results from the randomized, double-blind, placebo-controlled, Phase 3 trials U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT02819735), which demonstrated clinical remission in approximately 26% and 33% of patients taking upadacitinib 45 mg once daily for 8 weeks compared with placebo (5% and 4%). During the maintenance trial, 42% and 52% of patients treated with upadatinib 15 mg and 30 mg, respectively, achieved clinical remission at week 52, compared with 12% of patients in the placebo group. The patient also achieved glucocorticoid-free remission.

Initial approval for Crohn's disease based on three itemsThe results of phase 3 clinical trials include 2 induction studies U-EXCEED (NCT03345836) and U-EXCEL (NCT03344849), and 1 maintenance study U-ENDURE (NCT03345423). These trials evaluated the efficacy and safety of upadatinib 45 mg once daily as induction therapy and 15 and 35 mg upadatinib once daily as maintenance therapy in adults with moderately to severely active Crohn's disease. Across all 3 studies, researchers found that more participants who received upadacitinib met the co-primary endpoints of clinical remission and endoscopic response. Additionally, the researchers observed clinical remission as measured by the Crohn's Disease Activity Index based on patient-reported stool frequency/abdominal pain symptoms.

At AbbVie, we are committed to meeting the ongoing needs of patients with inflammatory bowel disease. Ulcerative colitis and Crohn's disease can affect every aspect of a patient's life. [Upadatinib] may be optionally prescribed to patients with moderately to severely active IBD following use of 1 approved systemic therapy, if the prescriber determines that a TNF blocker is not clinically advisable.

References:https://www.pharmacytimes.com/view/fda-approves-updated-indication-for-upadacitinib-in-patients-with-ibd