New anti-inflammatory drugs! Gilead JAK1 inhibitor filgotinib treatment of moderate active ulcerative colitis (UC) Phase III clinical success!

May 22, 2020 /
BiovalleyBIOON/-- Gilead Sciences and partner Galapagos recently jointly released the positive top-line results of the IIb/III SELECTION studyIn a randomized, double-blind, placebo-controlled study, adult patients who had not previously received biological agents (biologic-naive, biologic synod) or previously received biologics (biologic-biologics, biologics treated) were evaluating the efficacy and safety of the daily selective 1st-use inhibitor JAK1 filginibThe results showed that the filgotinib 200mg dose reached all the major endpoints of the study compared to placebo, including a significant increase in the proportion of patients who induced clinical remission at Week 10 and maintained clinical remission at Week 58The 100mg dose of filgotinib did not achieve a statistically significant difference in clinical remission rates at week 10SELECTION studies included 2 induction trials and one maintenance testThe cohort A induction test group was the first treatment patient of biologics, and the cohort B induction test group was the biologics treated patientsIn 2 induction trials, patients were randomly assigned 2:2:1 to receive filgotinib 200mg, 100mg, and placeboPatients who achieved clinical remission or clinical response at the 10th week of induction were re-randomized at a 2:1 ratio, receiving their induced dose of filgotinib or placebo, and treated until week 58Patients who completed the SELECTION study for 58 weeks were enrolled in the SELECTION long-term extended trial to assess the long-term safety of filgotinib in patients with moderate to severe active UCIn this trial, clinical remission was defined as: a mirror score of 0 or 1, a rectal hemorrhagic sub score of 0, and a decrease in the frequency of stool from the baseline to a score of 1, and a score of 0 or 1In the biologics initial treatment cohort (queue A induction trial; n-659), 52% of patients had a baseline Mayo clinical score (MCS) of 9In the biologics treatment cohort (queue B induction trial; n-689), 74% of patients had a baseline MCS score of 9, and 51% of patients had used 2 different biologicagents (TNF alpha antagonists and integrator receptor antagonists)data showed that the
proportion of patients who received clinical remission at the 10th week of treatment was statistically significantly higher (26.1% vs 15.3%, p.0157) in the first treatment patients of biologics (queue A), compared to the placebo groupIn biologic treated patients (queue B), the proportion of patients who received clinical remission at the 10th week of treatment in the 200mg dose of filgotinib also had a statistically significant increase (11.5% vs 4.2%, p.0103) compared to the placebo groupPatients whotreated with a dose of 100mg or 200mg filgotinib after 10 weeks of treatment to achieve clinical response or remission were subsequently randomly assigned to their induced dose of filgotinib or placebo at a ratio of 2:1 and treated until week 58 (maintenance test, n?558)Both doses of filgotinib reached the main endpoint of the maintenance trial: in the 58th week of treatment for first and treated patients with biologics, 37.2% of patients receiving 200 mg dose of filgotinib achieved clinical remission and the placebo group was 11.2% (p 0.0001)In 23.8% of patients treated with a 100 mg dose of filgotinib, clinical remission was achieved, and in the placebo group it was 13.5% (p-0.0420)in terms of safety, the incidence of severe adverse events was similar in each treatment group (200mg group: 1.2%; 100mg group: 4.7%; placebo group: 2.9%)In induction trials of patients treated with biologics, the incidence of severe adverse events was similar in each treatment group (200mg group: 7.3%; 100mg group: 5.3%; placebo group: 6.3%)There were no deaths in either induction queuein the maintenance trial, 4.5 percent of patients taking a 200 mg dose of filgotinib had severe adverse events, while the corresponding placebo group did not have severe adverse eventsIn 4.5% of patients taking a dose of 100mg filgotinib, 7.7% of patients in the corresponding placebo group had severe adverse eventsthe incidence of severe infection, shingles, venous thrombosis, pulmonary embolism and gastrointestinal perforation was low and comparable among the treatment groups during the induction and maintenance phase of the studyIn the maintenance trial, two deaths were observed in the filgotinib 200mg treatment groupAccording to the autopsy report, one patient with pre-asthma died fromasthmaworsening, and another patient with atherosclerosis died of left ventricular heart failureBoth deaths were assessed by the researchers as unrelated to the study of the drug ulcerative colitis (UC, picture: healthjade.com) Detailed results of the SELECTION study will be announced at a future medical conference "We are encouraged by filgotinib's early response to induction therapy and its continued efficacy as a maintenance therapy," said Dr Merdad Parsey, Chief Medical Officer, Gilead Patients with moderate to severe ulcerative colitis have difficulty in effectively controlling the condition These top line data suggest that filgotinib can play a role in helping more patients to achieve meaningful and sustained improvements in treatment response through oral therapy Dr Walid Abi-Saab, Chief Medical Officer, Galapagos, said: "We are pleased to see that the SELECTION study shows that filgotinib can help patients with ulcerative colitis, including those whose treatment is ineffective, to achieve and sustain the condition for more than a year We believe that the results show that the effectiveness and safety of the drug are consistent with previous studies and provide a meaningful contribution to patient data that use the drug in other inflammatory situations We look forward to presenting more detailed results to the scientific community "
ulcerative colitis (UC) is a chronic isoflame inflammatory disease that affects the colon, usually including the remission and activity period Common symptoms of UC are blood ycolites and rectal urgency Currently, there is no cure for UC, and most patients need to take the drug for life Clinically, the goal of UC treatment is to induce relief (to alleviate or asymptomatic) If this goal is achieved, maintenance therapy is required to prevent the recurrence of the disease It is estimated that 40% of patients relapse every year and do not achieve sustained remission filgotinib Molecular Structure (Photo: Wikipedia) filgotinib is a highly selective JAK1 inhibitor discovered and developed by Galapagos Gilead reached a $2 billion deal with Galapagos at the end of December 2015 to jointly develop filgotinib The partnership will help strengthen Gilead's position in the field of inflammatory diseases, which will also be a new growth point for Gilead in the future, following the hepatitis C and HIV fields December 2019, Gilead to the United States The FDA filed a new drug application for filgotinib
to treat rheumatoid arthritis (RA) It is worth mentioning that Gilead also submitted a priority review voucher to shorten the review time Filgotinib's treatment of RA indications is also under review by EU and Japanese regulators In addition to RA, both parties are also developing the drug for use in a variety of other inflammatory diseases, the treatment of Crohn's disease, ulcerative colitis has entered Phase III research pharmaceutical market research firm, Pharma Evaluate, had predicted that filgotinib would be one of Gilead's key products to drive future growth, with global sales expected to reach $1.4 billion by 2024 However, in the field of JAK inhibitors, filgotinib will also face a number of competing products, in addition to two listed products
Pfizer
Xeljanz and Lilly Olumiant, the stronger opponent will be AbbVie's Rinvoq, which has been approved by the United States and Europe to treat moderate to severe RA EvaluatePharma had also forecast sales of $2.57 billion in 2024 after Rinvoq went public (BioValleyBioon.com) original origin: Gilead and Galapagos Announce Positive Topline Results of Phase 2b/3 Trial of Filgotinib in Moderately Active Ulcer Colitis