Phase 2b/3 Trial Shows Efficacy of Filgotinib for the Induction and Maintenance of Remission in Moderately and Severely Active Ulcerative Colitis
-- Filgotinib 200mg Achieved Endoscopic, Histologic and Six-Month Corticosteroid-Free Remission at Week 58 with a Consistent Safety Profile --
-- Study Enrolled Biologic-Naïve and Biologic-Experienced Patients, a High Proportion of Whom Were Highly Refractory --
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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
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
“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.
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.
Filgotinib (200 mg and 100 mg tablets) is approved in
About the Filgotinib Collaboration
More information about clinical trials with filgotinib can be accessed at: www.clinicaltrials.gov.
Gilead Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors. There is also the possibility of unfavorable results from ongoing and additional clinical trials involving filgotinib, including the SELECTION long-term extension trial and the DIVERSITY trial. Further, it is possible that the parties may make a strategic decision to discontinue development of ﬁlgotinib for the treatment of ulcerative colitis or other indications, and as a result, filgotinib may never be successfully commercialized for the treatment of ulcerative colitis or other indications. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These risks, uncertainties and other factors could cause actual results to diﬀer materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Form 10-Q for the quarter ended
Galapagos Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, that are subject to risks, uncertainties and other factors that could cause actual results to diﬀer materially from those referred to in the forward-looking statements and, therefore, the reader should not place undue reliance on them. These risks, uncertainties and other factors include, without limitation, the risk that ongoing and future clinical studies with filgotinib may not be completed in the currently envisaged timelines or at all, the inherent uncertainties associated with competitive developments, clinical trial and product development activities and regulatory approval requirements (including that data from the ongoing and planned clinical research programs may not support registration or further development of filgotinib for ulcerative colitis or other indications due to safety, efficacy or other reasons), Galapagos' reliance on collaborations with third parties (including our collaboration partner for filgotinib, Gilead) and that Galapagos’ estimations regarding its filgotinib development program and regarding the commercial potential of filgotinib, may be incorrect, as well as those risks and uncertainties identified in our Annual Report on Form 20-F for the year ended
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