Results of phase IIb/III trial of filgotinib in moderately to severely active ulcerative colitis. Gilead Sciences + Galapagos NV

Gilead Sciences, Inc. and Galapagos NV announced positive topline results from SELECTION, a randomized, double-blind, placebo-controlled, Phase IIb/III trial evaluating the efficacy and safety of the investigational, oral, once-daily, selective JAK1 inhibitor filgotinib in 1,348 biologic-naïve or biologic-experienced adult patients with moderately to severely active ulcerative colitis (UC).

Filgotinib 200 mg achieved all primary endpoints in the study , inducing clinical remission at Week 10 and maintaining clinical remission at Week 58 in a significantly higher proportion of patients compared with placebo.Filgotinib 100 mg did not achieve statistically significant clinical remission at Week 10 .

In this trial, clinical remission was defined as an endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and greater than 1 point decrease in stool frequency from baseline to achieve a subscore of 0 or 1. Among the biologic-naïve cohort (Cohort A induction trial; n=659), 52 percent of patients had a baseline Mayo Clinic Score (MCS) of nine or higher. In the biologically-experienced cohort (Cohort B induction trial; n=689), 74 percent of patients had a baseline MCS of nine or higher, and 51 percent were previously treated with two different classes of biologics (TNF alpha antagonists and an integrin receptor antagonist).

Among biologic-naïve patients , a statistically significant higher proportion of patients achieved clinical remission at Week 10 when treated with filgotinib 200 mg (26.1 percent, p=0.0157) compared with placebo (15.3 percent). Among biologic-experienced patients, a statistically significant higher proportion of patients achieved clinical remission at Week 10 when treated with filgotinib 200 mg (11.5 percent, p=0.0103) compared with placebo (4.2 percent).

Patients who achieved clinical response or remission after 10 weeks of treatment with filgotinib 100 mg or 200 mg were subsequently re-randomized to their induction dose of filgotinib or placebo in a 2:1 ratio and treated through Week 58 (maintenance trial, n=558).Both doses of filgotinib achieved the primary endpoint in this maintenance trial . At Week 58, 37.2 percent of biologic-naïve and biologic-experienced patients receiving filgotinib 200 mg achieved clinical remission, compared with 11.2 percent treated with placebo (p?0.0001). Of patients receiving filgotinib 100 mg, 23.8 percent achieved clinical remission at Week 58, compared with 13.5 percent treated with placebo (p=0.0420).

In the induction trial of biologic-naïve patients , the incidence of serious adverse events was similar across treatment groups (200 mg: 1.2 percent; 100 mg: 4.7 percent; placebo: 2.9 percent). In the induction trial of biologic-experienced patients, the incidence of serious adverse events was also similar across treatment groups (200 mg: 7.3 percent; 100 mg: 5.3 percent; placebo: 6.3 percent). There were no deaths in either induction cohort. In the maintenance trial, 4.5 percent of patients treated with filgotinib 200 mg experienced a serious adverse event, compared with none for their corresponding placebo; 4.5 percent of patients treated with filgotinib 100 mg experienced a serious adverse event, compared with 7.7 percent for their corresponding placebo. Rates of serious infections, herpes zoster, venous thrombosis, pulmonary embolism and gastrointestinal perforation were low and comparable across treatment groups in both the induction and maintenance phases of the study. Two deaths were observed in the filgotinib 200 mg treatment group in the maintenance trial. One patient with pre-existing asthma died due to asthma exacerbation, and the second patient with pre-existing atherosclerosis died due to left ventricular heart failure per autopsy report. Neither death was assessed as related to study drug by the investigator.

About the SELECTION Phase IIb/III Trial: The SELECTION Phase IIb/III trial is a multi-center, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of the selective JAK1 inhibitor filgotinib in adult patients with moderately to severely active ulcerative colitis. The SELECTION trial comprises 2 Induction Trials and a Maintenance Trial. The Cohort A Induction Trial enrolled biologic-naive patients, and the Cohort B Induction Trial enrolled biologic-experienced patients. Across both induction studies, patients with moderately to severely active UC were randomized to receive filgotinib 200 mg, filgotinib 100 mg or placebo in a 2:2:1 ratio. Moderately to severely active UC was defined as a centrally read endoscopy score greater than 2, a rectal bleeding score greater than 1, a stool frequency score greater than 1 and Physician Global Assessment (PGA) of greater than 2 based on the MCS. Patients with clinical remission or response at Week 10 of induction were subsequently re-randomized to the induction dose of filgotinib or placebo in a 2:1 ratio and treated through Week 58.

The primary objectives of SELECTION are to evaluate the efficacy of filgotinib compared with placebo in establishing EBS clinical remission as determined by the Mayo Clinic endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and greater than 1 point decrease in stool frequency from baseline to achieve a subscore of 0 or 1 at Week 10 and Week 58. Eligible patients who completed treatment in the SELECTION trial through Week 58 were enrolled in the ongoing SELECTION long-term extension trial to evaluate the long-term safety of filgotinib in patients with moderately to severely active UC.