Gilead/Galapagos Oral JAK1 Inhibitor Jyseleca Shows Rapid Symptom Improvement and Sustained Steroid-Free Remission in Ulcerative Colitis

Ulcerative colitis (UC, image source: healthjade.com)

July 12, 2021 /BioonBIOON/ -- Galapagos NV, a partner of Gilead Sciences, recently presented new post-hoc analysis results from the Phase 3 SELECTION program for the oral anti-inflammatory drug Jyseleca (filgotinib, 200 mg) at the 16th Annual Congress of the European Crohn's and Colitis Organisation (ECCO).The data presented at the meeting support the efficacy and safety of Jyseleca, a once-daily oral JAK1 preferential inhibitor, in the treatment of patients with moderately to severely active ulcerative colitis (UC).

Jyseleca is an oral selective JAK1 inhibitor approved for marketing in the European Union, the United Kingdom, and Japan, for the treatment of moderate to severe conditions in patients with an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).ClassRheumatic arthritis（RA）Adult patients. Regarding administration, Jyseleca may be used as monotherapy or in combination with methotrexate (MTX). Currently, new indication applications for Jyseleca in the treatment of UC are also under regulatory review in the European Union, the United Kingdom, and Japan, specifically for: the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to, lost response to, or are intolerant to conventional therapy or biologics. It is worth noting that,Due to safety concerns, the United StatesFDANo indications have been approved for Jyseleca.

At this meeting, a post hoc analysis of the induction study data from the SELECTION program demonstrated that, in patients with moderate-to-severe active UC,Compared with placebo, filgotinib (200 mg orally once daily) significantly improved stool frequency (SF) and rectal bleeding (RB)., the efficacyObserved as early as the first week of treatment, and was observed in both biologic-naive (previously untreated with biologics) and biologic-experienced (previously treated with biologics) patients.

Compared with placebo, among patients receiving 200 mg filgotinib,A higher proportion of patients: achieved a composite response of RB = 0 and SF ≤ 1 as early as Day 9 in Induction Study A(Biologic-naïve: filgotinib 200 mg group 18.8%, placebo group 9.5%, p<0.05),In Induction Study B, a composite assessment of RB=0 and SF≤1 was achieved as early as Day 7.(Biologic-experienced; filgotinib 200 mg group, 10.7%; placebo group, 4.2%, p < 0.05).

A further post hoc analysis of the SELECTION maintenance study reported the proportion of patients achieving steroid-free remission at various time points. These data demonstrated that, compared with placebo, filgotinib (200 mg orally once daily) reduced and eliminated corticosteroid (CS) use at Week 58 in patients with moderately to severely active UC. Among patients who achieved CS-free remission at Week 58,Compared with the placebo group, a significantly higher proportion of patients in the filgotinib 200 mg group sustained corticosteroid-free remission through the first 6 months.(27% vs 6%), with the difference observed as early as the first 8 months (22% in the fingolimod 200 mg group vs 6% in the placebo group).

Additional safety analysis from the SELECTION program, pooling data from the induction, maintenance, and long-term extension studies (cumulative treatment exposure of 1,207 patient-years for filgotinib 200 mg and 318 patient-years for placebo),Safety results were consistent with the initial induction and maintenance studies, and filgotinib was well tolerated in patients with moderately to severely active UC.

Walid Abi Saab, Chief Medical Officer at Galapagos, stated: “Listening to the needs of patients with moderate to severe active UC and the healthcare professionals treating them has helped us understand the importance of finding a treatment that addresses both clinical symptoms and patient-reported outcomes. New data from the SELECTION and long-term extension studies show that, compared with patients receiving placebo, those with moderate to severe active UC treated with filgotinib 200 mg experienced rapid response, sustained steroid-free remission, and long-term tolerability.”

Filgotinib molecular structure (Image source: Wikipedia)

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). Its symptoms are often intermittent, so patients typically experience periods of flare and remission. In addition to its physical impact, the disease also exerts a significant psychological impact.

The active pharmaceutical ingredient of Jyseleca is filgotinib, a highly selective JAK1 inhibitor discovered and developed by Galapagos. In late December 2015, Gilead entered into an agreement with Galapagos valued at up to $2 billion to co-develop and commercialize filgotinib globally.Due to significant regulatory setbacks in the United States, the two parties revised the commercialization and development agreement for filgotinib in December 2020.Galapagos will be responsible for the commercialization of filgotinib in Europe (with the transition expected to be completed by the end of 2021), while Gilead will continue to be responsible for filgotinib in regions outside Europe, including Japan (where Gilead co-markets filgotinib with Eisai).

Currently, filgotinib is being developed for the treatment of various inflammatory diseases, with Phase 3 studies including the treatment ofRheumatic arthritis, Crohn's disease, ulcerative colitis. However, in the JAK inhibitor field, filgotinib also faces multiple competing products, in addition to the 2 marketed productsPfizerXeljanz andEli LillyBeyond Olumiant, a stronger competitor will be AbbVie's Rinvoq (upadacitinib).

It is worth noting that,In the first half of this year, the United StatesFDADelayed Review Timeline for New Indications of Multiple JAK Inhibitors, including Pfizer's abrocitinib for the treatment of moderate-to-severe atopic dermatitis (AD), Xeljanz/Xeljanz XR for the treatment of ankylosing spondylitis (AS), and Olumiant for the treatment of moderate-to-severe AD and active psoriatic arthritis (PsA).

The reason is that a post-marketing safety study published in January this year found that, compared with traditional older TNF inhibitors, Xeljanz increases the risk of serious cardiovascular diseases and cancer. Currently, the United StatesFDAA rigorous review is currently underway for all drugs in the JAK inhibitor class. The agency has requested relevant pharmaceutical companies to submit additional analytical data. (Bioon.com)

Original source:Galapagos announces new data supporting rapid symptom improvement and sustained steroid-free remission with filgotinib in patients with Ulcerative Colitis