Gilead Sciences, Inc. and Galapagos NV presented late-breaking data demonstrating sustained efficacy and safety with filgotinib, an investigational, oral, once-daily, JAK1 preferential inhibitor, for the treatment of moderately to severely active ulcerative colitis (UC). The data from the randomized, double-blind, placebo-controlled, Phase 2b/3 SELECTION trial showed that a significantly higher proportion of patients treated with filgotinib 200 mg, versus placebo, achieved clinical remission at Week 10 and maintained remission through Week 58. In addition, significantly more patients achieved six-month corticosteroid-free remission.
UC is a longer-term condition characterized by inflammation of the mucosal lining of the colon and rectum. An increasingly prevalent disease, UC has a significant impact on the quality of life of more than 2 million people around the world. Despite current treatments, many patients experience fecal urgency, incontinence, recurring bloody diarrhea, and the need to empty their bowels frequently, often accompanied by abdominal pain, poor sleep and fatigue.
“There remains a tremendous need for treatments that can achieve meaningful and sustained clinical outcomes in ulcerative colitis,” said Laurent Peyrin-Biroulet, MD, PhD, Gastroenterology Department at Lorraine University in France, and presenting investigator of the SELECTION maintenance study. “These study results showed that filgotinib reduced bleeding and stool frequency while also achieving remission across a range of measures, including endoscopy and histology, in an oral formulation.”
The SELECTION study included biologic-naïve patients, for whom prior conventional therapy had failed, as well as biologic-experienced patients, a high proportion of whom had been non-responders to at least two different lines of prior biologics. In total, 43 percent of patients in the biologic-experienced cohort had failed treatment with both a TNF inhibitor and vedolizumab. The study allowed the enrollment of patients who were taking steroids, and/or immunomodulators, including methotrexate, mercaptopurine (6-MP) or azathioprine, as they would in real-world clinical practice.
Efficacy Data of Filgotinib in Induction and Maintenance
Overall, 1,348 biologic-naïve or biologic-experienced adult patients with moderately to severely active UC were randomized and treated in the SELECTION study. Among biologic-naïve patients treated with filgotinib 200 mg, a significantly higher proportion of patients achieved clinical remission at Week 10 compared with placebo (26.1% vs. 15.3%, p=0.0157). Additionally, a significantly higher proportion of biologic-naïve patients treated with filgotinib 200 mg versus placebo achieved 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). A significantly higher proportion of biologic-experienced patients treated with filgotinib 200mg achieved clinical remission at Week 10 compared with placebo (11.5% vs. 4.2%, p=0.0103).
Patients treated with filgotinib who achieved clinical response or remission at Week 10 were re-randomized to their induction dose of filgotinib or placebo in a 2:1 ratio and treated through Week 58 (Maintenance Trial, n=558). At Week 58, 37.2 percent of patients receiving filgotinib 200 mg achieved clinical remission, compared with 11.2 percent of patients treated with placebo (p˂0.0001). A significantly higher proportion of those treated with filgotinib 200 mg versus placebo achieved sustained clinical remission (18.1% vs. 5.1%, p=0.0024), MCS remission (34.7% vs. 9.2%, p<0.0001), endoscopic remission (15.6% vs. 6.1%, p=0.0157) and histologic remission (38.2% vs. 13.3%, p<0.0001). Additionally, a significantly higher proportion of patients treated with filgotinib 200 mg achieved six-month corticosteroid-free clinical remission at Week 58 compared with placebo (27.2% vs. 6.4%, p=0.0055).
Safety Outcomes with Filgotinib in Ulcerative Colitis
Overall, the incidence of adverse events (AEs), serious AEs and discontinuations due to AEs were similar in the filgotinib and placebo groups in both the induction and maintenance periods of the study. Serious infections, herpes zoster, venous thrombosis, pulmonary embolism and gastrointestinal perforation were infrequent and comparable across treatment groups. The most common adverse events of interest in the induction trials were serious infections (1.1% filgotinib 100 mg, 0.6% filgotinib 200 mg, 1.1% placebo), herpes zoster (0.2% filgotinib 100 mg, 0.6% filgotinib 200 mg, 0.0% placebo), opportunistic infections (0.0% filgotinib 100 mg, 0.2% filgotinib 200 mg, 0.0% placebo) and pulmonary embolism (0.0% filgotinib 100 mg, 0.2% filgotinib 200 mg, 0.0% placebo). In the maintenance trial, the most common adverse events of interest were serious infections (1.7% filgotinib 100 mg, 1.0% filgotinib 200 mg, 1.1% placebo), herpes zoster (0.0% filgotinib 100 mg, 0.5% filgotinib 200 mg, 0.0% placebo) and venous thrombosis (0.0% filgotinib 100 mg, 0.0% filgotinib 200 mg, 2.2% placebo). Two deaths were observed in the filgotinib 200 mg treatment group in the maintenance trial; both adverse events leading to deaths were considered by the study investigators to be unrelated to study drug.
“Ulcerative colitis is a complex and unpredictable condition that can impact people in the prime of their lives. Despite treatment, people with UC can experience symptoms that have a significant impact on their quality of life,” said Mark Genovese, MD, Senior Vice President, Inflammation, Gilead Sciences. “We are pleased to share these data on the use of filgotinib in UC as we work to identify new treatment options to address unmet needs across a range of inflammatory diseases.”
“The SELECTION study assessed the efficacy and safety of filgotinib in some of the most difficult-to-treat patients with ulcerative colitis, including a high proportion of patients who were refractory to biologic treatment and in need of new treatment options,” said Dr. Walid Abi-Saab, Chief Medical Officer, Galapagos. “The efficacy and safety data seen with filgotinib in this patient population add to the growing body of evidence demonstrating the potential this once-daily treatment may offer patients living with this debilitating condition.”
About the SELECTION Phase 2b/3 Trial
The SELECTION Phase 2b/3 trial is a multi-center, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of the JAK1 preferential inhibitor, filgotinib in adult patients with moderately to severely active UC. The SELECTION trial comprises two induction trials and a maintenance trial. The Induction Study A enrolled biologic-naïve patients, and the Induction Study B 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 ≥ 2, a rectal bleeding score ≥ 1, a stool frequency score ≥ 1 and Physician Global Assessment (PGA) of ≥ 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 were to evaluate the efficacy of filgotinib compared with placebo in establishing clinical remission as determined by the Mayo endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and ≥ 1-point decrease in stool frequency from baseline to achieve a subscore of 0 or 1 at Week 10 in the induction studies and Week 58 in the maintenance study. Eligible patients who were enrolled in the SELECTION trial 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.