Gilead and Galapagos Announce Positive Phase 2b/3 Results for JAK1 Inhibitor Filgotinib in Ulcerative Colitis, Demonstrating Sustained Remission

Today, Gilead Sciences and Galapagos jointly announced that filgotinib, an oral JAK1-selective inhibitor co-developed by the two companies, demonstrated durable efficacy and safety in Phase 2b/3 clinical trials for the treatment of moderately to severely active ulcerative colitis (UC). Compared with placebo, a significantly higher proportion of patients treated with 200 mg of filgotinib achieved clinical remission at Week 10 and maintained remission through Week 58.

Ulcerative colitis (UC) is a chronic, long-term disease characterized by inflammation of the mucosa in the colon and rectum. As an increasingly prevalent condition, UC significantly impacts the quality of life for over 2 million people worldwide. Despite treatment with currently available therapies, many patients continue to experience fecal urgency, incontinence, and recurrent episodes of bloody diarrhea, often accompanied by abdominal pain, poor sleep, and fatigue.

Filgotinib is a selective JAK1 inhibitor co-developed by Gilead Sciences and Galapagos. JAK kinase-dependent cytokines are associated with the pathogenesis of many inflammatory and autoimmune diseases. This characteristic suggests that JAK inhibitors can be used to treat various inflammatory conditions. In September this year, filgotinib was simultaneously approved in the European Union and Japan for the treatment of patients with moderate to severe active rheumatoid arthritis.

▲Molecular structure of filgotinib (Image source: Vaccinationist / Public domain)

In the SELECTION randomized, double-blind, placebo-controlled Phase 2b/3 clinical trial, a total of 1,348 adult patients with moderately to severely active ulcerative colitis (UC) were randomly assigned to receive filgotinib or placebo. These patients were stratified into biologic-naïve and biologic-experienced groups based on prior exposure to biologic agents. Among patients who had not previously received biologic therapy, the proportion achieving clinical remission at Week 10 was significantly higher in the group receiving filgotinib 200 mg than in the placebo group (26.1% vs. 15.3%, p=0.0157).

Furthermore, compared with placebo, biologic-naïve patients treated with 200 mg filgotinib achieved significantly higher rates of Mayo Clinic Score (MCS) remission (24.5% vs. 12.4%, p=0.0053), endoscopic remission (12.2% vs. 3.6%, p=0.0047), and histologic remission (35.1% vs. 16.1%, p<0.0001).

Among patients who had previously received biologic therapy, the proportion of those treated with 200 mg filgotinib achieving clinical remission at Week 10 was also significantly higher (11.5% vs. 4.2%, p=0.0103).

Patients who received filgotinib and achieved clinical response or remission at Week 10 were re-randomized in a 2:1 ratio to receive either the induction dose of filgotinib or placebo, with treatment continuing through Week 58 (maintenance trial, n=558). At Week 58, 37.2% of patients treated with 200 mg filgotinib achieved clinical remission, compared with 11.2% of those receiving placebo (p<0.0001). Furthermore, the proportion of patients treated with 200 mg filgotinib who achieved glucocorticoid-free clinical remission sustained for 6 months at Week 58 was significantly higher than that in the placebo group (27.2% vs. 6.4%, p=0.0055).

References:

[1] Phase 2b/3 Trial Shows Efficacy of Filgotinib for the Induction and Maintenance of Remission in Moderately and Severely Active Ulcerative Colitis. Retrieved October 12, 2020, from https://www.businesswire.com/news/home/20201012005470/en

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