American biopharmaceutical company Gilead Sciences (Nasdaq: GILD) and Belgian Galapagos NV (Euronext & Nasdaq: GLPG) have announced positive top-line results from the SELECTION phase 2b/3 clinical trial, which evaluated the safety and efficacy of the selective JAK1 inhibitor filgotinib for the treatment of adults with moderate-to-severe ulcerative colitis (UC).
Gilead Chief Medical Officer Merdad Parsey, MD, PhD, stated, “We are encouraged by the early response as an induction therapy and the durable efficacy as a maintenance therapy observed in the SELECTION trial. Patients with moderate to severe ulcerative colitis can struggle to effectively manage their disease. These topline data suggest that filgotinib could play a role in helping more patients achieve a meaningful and sustained improvement in treatment response with an oral therapy.”
“We are pleased to see that SELECTION results indicate that filgotinib can help ulcerative colitis patients, including those refractory to treatment, achieve and sustain remission for more than one year. We believe that the results point to an efficacy and safety profile consistent with prior studies with filgotinib, and offer a meaningful contribution to the patient data with filgotinib from other inflammatory conditions. We look forward to presenting more detailed results to the scientific community,” said Dr. Walid Abi-Saab, Chief Medical Officer of Galapagos.
The randomized, double-blind, placebo-controlled, multi-center SELECTION clinical trial incorporated 1,348 adults with active UC divided into three studies: two induction and one maintenance. Patients were sorted into the induction studies based on their history of treatment with biologics (“naïve” or “experienced”). Among both induction studies, patients with moderate-to-severe active UC “were randomized to receive filgotinib 200 mg, filgotinib 100 mg or placebo in a 2:2:1 ratio.”
The primary objective of the Gilead SELECTION trial was to evaluate the comparative efficacy of filgotinib and a placebo for inducing disease remission as measured by clinical indices of endoscopy, rectal bleeding, and stool frequency.
In the Gilead trial, Filgotinib “achieved all primary endpoints” at a dose of 200 mg, “inducing clinical remission at Week 10 and maintaining clinical remission at Week 58 in a significantly higher proportion of patients compared with placebo.” The 100 mg dose “did not achieve statistically significant clinical remission at Week 10.”
Filgotinib is a selective inhibitor of JAK1, a tyrosine kinase protein important for intracellular signaling events certain populations of immune cells. UC is a debilitating chronic inflammatory autoimmune disorder affecting the colon that often involves fluctuation between periods of remission and periods of active inflammation (“flares”).
According to the press release, “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.”
“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.”
In addition to ulcerative colitis, filgotinib is being evaluated by Gilead for the treatment of other inflammatory conditions including rheumatoid arthritis (FINCH Phase 3 trial), Crohn’s disease (DIVERSITY Phase 3 trial), psoriatic arthritis (PENGUIN phase 3 trials), uveitis (phase 2 trial), and small bowel and fistulizing Crohn’s disease (phase 2 trial).
To understand the implications of COVID-19 for Ulcerative colitis and Crohn’s Disease patients, check out our interview of Professor of Gastroenterology Dr. Giovanni Monteleone from the University of Rome Tor Vergata.