Filgotinib Achieves Primary Endpoints in Phase 2b/3 SELECTION Trial for Moderately to Severely Active Ulcerative Colitis

Compiled by S.Li

Recently, Gilead and Galapagos jointly announced that filgotinib, an oral JAK inhibitor co-developed by the two companies, achieved positive results in the Phase 2b/3 SELECTION clinical trial. This randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of filgotinib in 1,348 adult patients with moderate-to-severe ulcerative colitis (UC), who were either biologic-experienced or biologic-naïve.

The results showed that the Filgotinib 200 mg dose group achieved all primary endpoints of the study, with patients in this treatment group achieving clinical remission at Week 10 and maintaining remission for 58 weeks. However, at Week 10, the Filgotinib 100 mg dose group did not achieve statistically significant clinical remission.

Specifically, among patients who had not previously received biologic therapy, a significantly higher proportion of patients in the filgotinib 200 mg group achieved clinical remission at Week 10 compared with placebo (26.1% vs. 15.3%; p=0.0157). Among patients who had previously received biologic therapy, the proportion of patients achieving clinical remission at Week 10 was also significantly higher in the filgotinib 200 mg group (11.5% vs. 4.2%; p=0.0103).

Patients who achieved clinical remission after 10 weeks in the two filgotinib dose groups were subsequently randomized in a 2:1 ratio to receive either filgotinib or placebo at the induction therapy dose, continuing through Week 58 (maintenance trial; n=558). The results demonstrated that both doses of filgotinib met the primary endpoint of the maintenance trial. At Week 58, 37.2% of patients in the 200 mg filgotinib group achieved clinical remission, compared with 11.2% in the placebo group (p<0.0001); in the 100 mg filgotinib group, 23.8% of patients achieved clinical remission at Week 58, versus 13.5% in the placebo group (p=0.0420).

In this trial, clinical remission was defined as an endoscopic subscore of 0 or 1, a rectal bleeding subscore of 0, and a reduction in stool frequency from ≥1 at baseline to a score of 0 or 1. Among patients who had not previously received biologic therapy, 52% had a baseline Mayo Clinic Score (MCS) of 9 or higher. Among patients who had previously received biologic therapy, 74% had a baseline MCS of 9 or higher, and 51% had been treated with two different classes of biologics (TNF-α antagonists and integrin receptor antagonists).

In the induction trial, no deaths occurred in any treatment group. The incidence of serious adverse events was similar among patients who had not received prior biologic therapy (200 mg: 1.2%; 100 mg: 4.7%; placebo: 2.9%). Among patients who had received prior biologic therapy, the incidence rates were also similar across all dose groups and the placebo group (200 mg: 7.3%; 100 mg: 5.3%; placebo: 6.3%). In the maintenance trial, there were no drug-related deaths. The proportion of patients experiencing serious adverse events was 4.5% in the filgotinib 200 mg treatment group, compared with 0% in the corresponding placebo group. The proportion of patients experiencing serious adverse events was 4.5% in the filgotinib 100 mg treatment group, compared with 7.7% in the corresponding placebo group.

Dr. Merdad Parsey, Chief Medical Officer of Gilead Sciences, stated, “We are encouraged by the early response to filgotinib as induction therapy and its durable efficacy as maintenance therapy in the SELECTION trial. These important data demonstrate that filgotinib can help more patients achieve meaningful and sustained treatment responses with an oral therapy.”

Ulcerative colitis (UC) and Crohn’s disease (CD) are the two most common forms of inflammatory bowel disease (IBD). Both are chronic, relapsing, and spontaneously remitting inflammatory progressive disorders of the gastrointestinal tract. It is estimated that 40% of patients with UC experience annual relapses and fail to achieve sustained remission.

Filgotinib is a drug co-developed by Gilead Sciences and Galapagos. New Drug Applications (NDAs) for its use in adult patients with moderately to severely active rheumatoid arthritis have been submitted to the U.S. Food and Drug Administration (FDA) and the Japanese Ministry of Health, Labour and Welfare (MHLW), and are currently under review. In addition to the SELECTION trial, Filgotinib is undergoing multiple clinical studies for inflammatory diseases, including the Phase 3 FINCH trial for rheumatoid arthritis, the Phase 3 DIVERSITY trial for Crohn’s disease, and the Phase 3 PENGUIN trial for psoriatic arthritis.

Reference Source: Gilead and Galapagos Announce Positive Topline Results of Phase 2b/3 Trial of Filgotinib in Moderately to Severely Active Ulcerative Colitis