Gilead Sciences and Galapagos reported top-line results Wednesday demonstrating that the higher dose of their once-daily investigational JAK1 inhibitor filgotinib achieved all primary endpoints of a Phase IIb/III study in patients with moderately to severely active ulcerative colitis (UC). "We are encouraged by the early response as an induction therapy and the durable efficacy as a maintenance therapy observed in the SELECTION trial," said Merdad Parsey, chief medical officer at Gilead, adding that the findings suggest "filgotinib could play a role in helping more patients achieve a meaningful and sustained improvement in treatment response with an oral therapy."
The trial enrolled 1348 biologic-naïve or biologic-experienced adults with moderately to severely active UC who were randomised to receive one of two doses of filgotinib or placebo. Subjects with clinical remission or response at week 10 of induction were subsequently re-randomised to the induction dose of filgotinib or placebo, and treated through to week 58. The primary objectives assessed the efficacy of filgotinib against placebo in establishing endoscopy, rectal bleeding and stool frequency (EBS) clinical remission, defined as a Mayo Clinic endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and at least a 1-point decrease in stool frequency from baseline to achieve a subscore of 0 or 1 at weeks 10 and 58.
Results showed that the higher 200-mg dose of filgotinib achieved all primary endpoints in the study, inducing clinical remission at week 10, and maintaining that through to week 58. Specifically, among biologic-naïve patients, 26.1% of patients were in clinical remission at week 10 when treated with filgotinib 200 mg, versus 15.3% for placebo, while among biologic-experienced patients, the rates were 11.5% and 4.2%, respectively.
Patients who achieved clinical response or remission after 10 weeks of treatment with either of the filgotinib doses were then re-randomised to their induction dose of filgotinib or placebo, and treated through week 58. Gilead and Galapagos said both doses of filgotinib achieved the primary endpoint in this maintenance portion of the trial. Specifically, 37.2% of biologic-naïve and biologic-experienced patients in the higher-dose group achieved clinical remission, compared with 11.2% for placebo. For those in the lower-dose group, 23.8% achieved clinical remission at week 58, compared with 13.5% for placebo. Detailed results from the SELECTION trial will be submitted for presentation at a future scientific conference.
In terms of safety, the companies noted that 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 higher-dose filgotinib group in the maintenance trial. According to the companies, one patient with pre-existing asthma died due to asthma exacerbation, while the second patient had pre-existing atherosclerosis and died due to left ventricular heart failure. Neither case was deemed related to the study drug.
In 2015, Gilead entered into a partnership with Galapagos potentially worth more than $2 billion to develop and market filgotinib for inflammatory diseases. Last year, it agreed to pay $3.95 billion upfront and make an equity investment of $1.1 billion as part of a 10-year R&D collaboration with Galapagos. Regulatory submissions of filgotinib for the treatment of rheumatoid arthritis are currently under review by regulators in the US, Europe and Japan.
For related analysis, see Spotlight On: Three key trends to watch in the rheumatoid arthritis market. See also ViewPoints: Filgotinib’s case for differentiation remains a work in progress.
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