Gilead's JAK1 Inhibitor Filgotinib Receives FDA Complete Response Letter for Rheumatoid Arthritis, $80 Million Priority Review Voucher Wasted

August 19, 2020 /BioValleyBIOON/ -- Gilead Sciences recently announced that the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) regarding the New Drug Application (NDA) for filgotinib (200 mg and 100 mg tablets). This drug is an oral selective JAK1 inhibitor indicated for the treatment of moderate to severe active rheumatoid arthritis.Rheumatoid Arthritis(RA) Adult patients.

Notably, when submitting the New Drug Application (NDA) to the FDA in December 2019, Gilead Sciences also utilized 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 Complete Response Letter (CRL) also means that the $80 million investment has gone to waste.

The FDA has requested data from the MANTA and MANTA-RAy studies. Patient enrollment for these two studies has been completed, aiming to evaluate whether filgotinib affects sperm parameters, with top-line results expected to be announced in the first half of 2021. In addition,FDAConcerns were also expressed regarding the overall benefit/risk profile of the 200 mg dose of filgotinib.

Merdad Parsey, M.D., Chief Medical Officer of Gilead Sciences, stated, “We are deeply disappointed by this FDA outcome and will evaluate the points raised in the CRL in order toFDAto discuss. We remain firmly convinced that filgotinib in the classRheumatoid Arthritistherapeutic benefits/risks, which has been demonstrated in the FINCH Phase III clinical program.”

Currently, filgotinib is also under review by regulatory authorities worldwide. In the European Union, at the end of July this year, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion, recommending the approval of Jyseleca (filgotinib, 100 mg and 200 mg tablets) for the treatment of adult patients with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response to or intolerance of one or more disease-modifying antirheumatic drugs (DMARDs). The CHMP’s positive opinion has been submitted to the European Commission (EC) for review, which is expected to make a final approval decision in the third quarter of this year.

The NDA for filgotinib is based on 52-week data from the global Phase III FINCH clinical program. This program evaluated the efficacy and safety of filgotinib in 3,452 patients with moderate to severe active rheumatoid arthritis (RA). In these studies, filgotinib met its primary endpoints and demonstrated sustained efficacy and long-term safety across a broad population of RA patients, including those with an inadequate response to methotrexate (MTX), those intolerant to one or more biologic agents, and MTX-naïve patients. Across various RA patient subgroups, once-daily oral filgotinib improved clinical signs and symptoms, achieved low disease activity and remission, and inhibited structural damage. Safety results were consistent throughout the FINCH program, further reinforcing the long-term safety and tolerability of filgotinib in a broad RA patient population.

Molecular structure of filgotinib (Image source: Wikipedia)

Despite the availability of current therapies, classRheumatoid Arthritis(RA) patients may face persistent disease symptoms and an inadequate response to existing treatments. One in five patients does not achieve complete disease remission during their lifetime and still requires treatment regimens.

Filgotinib is 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, to co-develop 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 hepatitis C and HIV.

Currently, Gilead Sciences and Galapagos are conducting multiple studies to evaluate the potential of filgotinib in treating various inflammatory diseases, with Phase III trials focusing on rheumatoid arthritis (RA), Crohn’s disease, and ulcerative colitis. Pharmaceutical market research firm EvaluatePharma previously released a report predicting that filgotinib will become one of the key products driving Gilead’s future growth, with global sales expected to reach $1.4 billion by 2024.

However, in the field of JAK inhibitors, filgotinib will also face multiple competing products, in addition to two already marketed products.PfizerXeljanz andEli LillyBeyond Olumiant, a more formidable competitor will be AbbVie’s Rinvoq (upadacitinib). Currently, Rinvoq has successfully received approval in the United States and the European Union for the treatment of moderate-to-severe rheumatoid arthritis (RA). EvaluatePharma previously predicted that Rinvoq’s sales would reach $2.57 billion in 2024 following its market launch. (Bioon.com)

Original Source: Gilead Receives Complete Response Letter for Filgotinib for the Treatment of Moderately to Severely Active Rheumatoid Arthritis