Gilead Submits New Drug Application in Japan for Jyseleca (Filgotinib) to Treat Ulcerative Colitis

April 24, 2021 News /BioValleyBIOON/ -- Gilead and Eisai recently jointly announced that they have submitted to the Japanese Pharmaceuticals and Medical Devices AgencyMedical DevicesAn application was submitted to the Pharmaceuticals and Medical Devices Agency (PMDA) seeking approval for a new indication of Jyseleca (filgotinib, 200 mg) for the treatment of patients with moderately to severely active ulcerative colitis (UC). Currently, the new indication of Jyseleca for UC is also under regulatory review in the European Union.

Jyseleca is an oral selective JAK1 inhibitor that was approved in the European Union and Japan on the same day in September 2020. In the European Union, the indication for Jyseleca is: for the treatment of moderate to severe rheumatoid arthritis in patients who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).Rheumatoid Arthritis(RA) adult patients. In Japan, the indication for Jyseleca is: for the treatment of RA patients with an inadequate response to conventional therapy, including the prevention of structural joint damage. Regarding administration, Jyseleca can be used as monotherapy or in combination with methotrexate (MTX).

Under the collaboration agreement reached in December 2019, Gilead Sciences K.K. holds the marketing authorization for Jyseleca in Japan, while Eisai Co., Ltd. is responsible for distributing the drug in Japan for the treatment of rheumatoid arthritis (RA) and other potential future indications, including ulcerative colitis, Crohn’s disease, and psoriatic arthritis.

Notably, regarding U.S. regulatory matters, the FDA issued a Complete Response Letter (CRL) in August 2020, declining to approve Jyseleca. The FDA has requested data from the MANTA and MANTA-RAy studies. Patient enrollment for these two studies has been completed; they are designed to assess whether filgotinib affects sperm parameters, with top-line results expected to be announced in the first half of 2021. Furthermore, the FDA expressed concerns about the overall benefit/risk profile of the 200 mg dose of filgotinib. In December 2019, toFDAUpon submitting the NDA, Gilead Sciences used a Priority Review Voucher (PRV) to expedite the review process. This PRV was acquired by Gilead from Ultragenyx for $80 million. The issuance of the CRL also means that the $80 million investment has gone down the drain.

UC (Image source: healthjade.com)

Ulcerative Colitis (UC) is a chronic, long-term condition that affects more than 2 million people in the European Union alone. The symptoms of this disease are often intermittent, so patients typically experience periods of flare-ups and remission.

The application for the new indication of Jyseleca in the treatment of UC is supported by data from the Phase 2b/3 SELECTION study. This was a randomized, double-blind, placebo-controlled study conducted in 1,348 adult patients with moderately to severely active UC who were either biologic-naïve (not previously treated with biologics) or biologic-experienced (previously treated with biologics).

The results showed that Jyseleca 200 mg met all primary endpoints of the study, including a statistically significantly higher proportion of patients achieving clinical remission at Week 10 and maintaining clinical remission through Week 58 compared with the placebo group. Furthermore, the proportion of patients in the Jyseleca 200 mg group who achieved endoscopic and histologic remission as well as corticosteroid-free remission for 6 months at Week 58 was statistically significantly higher than that in the placebo group.

Molecular Structure of Filgotinib (Image Source: Wikipedia)

The active pharmaceutical ingredient of Jyseleca is filgotinib, a highly selective JAK1 inhibitor discovered and developed by Galapagos. In late December 2015, Gilead Sciences entered into an agreement with Galapagos valued at up to $2 billion for the co-development of filgotinib. This collaboration will help strengthen Gilead’s position in the field of inflammatory diseases, which is poised to become a new growth driver for the company following its success in the hepatitis C and HIV sectors.

Currently, Gilead and Galapagos are conducting multiple studies to evaluate the potential of Jyseleca in treating various inflammatory diseases, including Phase III studies for the treatment ofRheumatoid Arthritis, Crohn's disease, and ulcerative colitis. The pharmaceutical market research firm EvaluatePharma previously released a report predicting that Jyseleca would become one of the key products driving Gilead's future growth, with global sales expected to reach $1.4 billion in 2024.

However, in the field of JAK inhibitors, Jyseleca will also face competition from multiple products, in addition to the two already marketed.PfizerXeljanz andEli LillyBeyond Olumiant, a more formidable competitor will be AbbVie’s Rinvoq (upadacitinib). Currently, Rinvoq has been approved for three indications: rheumatoidRheumatoid Arthritis(Rheumatoid Arthritis [RA]), Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS).

Notably, just recently, the United StatesFDADeferred the review of new indications for multiple JAK inhibitors, including Pfizer’s abrocitinib for moderate-to-severe atopic dermatitis (AD), Xeljanz/Xeljanz XR for ankylosing spondylitis (AS), Olumiant for moderate-to-severe AD, and Rinvoq for 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 heart-related conditions and cancer. Currently, the United StatesFDAStrict Review Underway for All Drugs in the JAK Inhibitor Class; Agency Requests Additional Analytical Data from Relevant Pharmaceutical Companies (Bioon.com)

Original Source: Gilead Sciences submits new drugapplication in Japan for filgotinib for the treatment of ulcerative colitis with an inadequate response to conventional therapies