U.S. & E.U. Differ on Filgotinib for RA

Filgotinib (Jyseleca) is a selective JAK1 inhibitor designed to be taken once daily in 100 or 200 mg tablets. The agent has been studied to treat adults with moderate to severe rheumatoid arthritis (RA) who are intolerant of one or more disease-modifying anti-rheumatic drugs (DMARDs) or for whom DMARDs are inadequate. Recently, the U.S. and E.U. issued differing statements regarding its use for RA patients.

In August, the U.S. Food & Drug Administration (FDA) sent Gilead, the manufacturer of filgotinib, a complete response letter on its new drug application for adults with moderate to severe, active RA, expressing concern about the overall risk/benefit profile of the 200 mg dose of filgotinib and asking for more data.^1,2

The FDA requested data from two additional clinical trials, MANTA and MANTA-RAy, prior to completing its application review. Among other factors, these studies will assess the treatment’s effect on sperm parameters and filgotinib’s risk/benefit profile. The results from MANTA and MANTA-RAy are expected in the first half of 2021. It’s unlikely Gilead will be able to refile the FDA application until the middle of next year, setting back the potential U.S. approval of this agent.

However, in late July, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use issued a positive opinion of filgotinib to the European Commission.³ The opinion serves as a scientific recommendation to the EMA to grant marketing authorization for filgotinib in Europe. The agency can authorize medication use in 27 E.U. countries, plus Norway, Iceland, Liechtenstein and the U.K.

The EMA recommendation is supported by data from the phase 3 FINCH and phase 2 DARWIN trials, in which researchers studied participants for 52 weeks. These trials encompassed 4,544 RA patient-years of experience with filgotinib.

Filgotinib-treated patients met the primary study endpoints in all three FINCH trials, consistently achieving ACR20, 50 and 70 treatment targets (i.e., improvement of 20%, 50% or 70% in the number of tender and swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure, visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein [CRP]), as well as other targets. Participants also achieved a Disease Activity Score for RA with CRP in 28 joints (DAS-28-CRP) of less than 2.6. Additionally, when compared with placebo, treatment with filgotinib inhibited the progression of structural joint damage, as assessed by the modified total Sharp score.

Safety profiles were consistent in the FINCH and DARWIN trials when filgotinib was administered with methotrexate or as monotherapy. Serious infections and herpes zoster rates for filgotinib were similar to those for adalimumab and methotrexate in RA patients. Major adverse cardiac events and venous thromboembolism were infrequently reported.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Gilead Sciences Inc. News release: Gilead receives complete response letter for filgotinib for the treatment of moderately to severely active rheumatoid arthritis. 2020 Aug 18.
2. Taylor NP. FDA rejects Gilead’s would-be blockbuster filgotinib over toxicity concerns. Fierce BioTech. 2020 Aug 19.
3. Gilead Sciences Inc. News release: Gilead and Galapagos announce positive European CHMP opinion for Jyseleca (filgotinib) for the treatment of adults with moderate to severe rheumatoid arthritis. 2020 Jul 24.