FOSTER CITY, Calif. & MECHELEN, Belgium—Gilead Sciences, Inc. and Galapagos NV have presented late-breaking data demonstrating sustained efficacy and safety with filgotinib, an investigational JAK1 preferential inhibitor, for the treatment of moderately to severely active ulcerative colitis (UC).
The data from the 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 their remission through Week 58. As well, significantly more patients achieved six-month corticosteroid-free remission.
The full results were presented at the 2020 United European Gastroenterology Week (UEGW) Virtual Meeting.
“There remains a tremendous need for treatments that can achieve meaningful and sustained clinical outcomes in ulcerative colitis,” said Laurent Peyrin-Biroulet, M.D., Ph.D., department of Gastroenterology 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.”
UC is a chronic condition, characterized by inflammation of the mucosal lining of the colon and rectum. Despite current treatments, many patients experience fecal urgency, incontinence, recurring bloody diarrhea and a frequent need to empty their bowels. This is often accompanied by abdominal pain, poor sleep and fatigue.
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 biologics. 43 percent of patients in the biologic-experienced cohort had failed treatment with both a TNF inhibitor and vedolizumab. The study also 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.
“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,” added Mark Genovese, M.D., senior vice president of Inflammation at 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,”
1,348 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 percent vs. 15.3 percent). A significantly higher proportion of biologic-naïve patients treated with filgotinib 200 mg versus placebo also achieved Mayo Clinic Score (MCS) remission (24.5 percent vs. 12.4 percent), endoscopic remission (12.2 percent vs. 3.6 percent) and histologic remission (35.1 percent vs. 16.1 percent). And a significantly higher proportion of biologic-experienced patients treated with filgotinib 200mg achieved clinical remission at Week 10, compared with placebo (11.5 percent vs. 4.2 percent).
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.
A significantly higher proportion of those treated with filgotinib 200 mg versus placebo achieved sustained clinical remission (18.1 percent vs. 5.1 percent), MCS remission (34.7 percent vs. 9.2 percent), endoscopic remission (15.6 percent vs. 6.1 percent) and histologic remission (38.2 percent vs. 13.3 percent). And 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 percent vs. 6.4 percent).
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. AEs were infrequent and comparable across treatment groups.
The most common AEs in the induction trials were serious infections, herpes zoster, opportunistic infections and pulmonary embolism. In the maintenance trial, the most common AEs were serious infections, herpes zoster and venous thrombosis. Two deaths were observed in the filgotinib 200 mg treatment group in the maintenance trial; both AEs that led to deaths were considered by the study investigators to be unrelated to filgotinib.
“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,” noted Dr. Walid Abi-Saab, chief medical officer of 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.”