UK panel backs filgotinib for RA despite FDA rejection
Undeterred by the FDA’s rejection of filgotinib over testicular toxicity concerns, the United Kingdom’s National Institute for Health and Clinical Excellence has endorsed its use among eligible patients on England’s National Health Service.
With this recommendation, Gilead Sciences/Galapagos NV’s filgotinib — approved under the tradename Jyseleca in Europe and Japan — will be available to patients with moderate-to-severe rheumatoid arthritis who have responded inadequately to previous therapy with two or more disease-modifying antirheumatic drugs.
“This is a landmark decision from NICE and represents a pivotal moment for the treatment of RA,” James Galloway, PhD, MSc, senior lecturer at King’s College Hospital, said in a press release. “The goals of treatment in this condition are to control pain, prevent disability and improve quality of life. This requires us to act quickly to control the disease, preventing irreversible joint damage as soon as possible, for as long as possible.”
“While no single medicine works for everyone, the addition of filgotinib is an important step forward that we believe will help more patients achieve remission, even when their disease is at a less advanced stage,” he added. “This is welcome news that should allow people across the UK to have more time free from the pain and distress RA is capable of causing.”
Different view stateside
NICE issued its final appraisal determination for filgotinib based on results of the phase 3 FINCH and phase 2 DARWIN trials – the same results that spurred the FDA to reject filgotinib over “concerns regarding the overall benefit/risk profile of the filgotinib 200 mg dose,” as reported in a Gilead release.
Although filgotinib had already obtained a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use for the treatment of moderate-to-severe RA, the FDA requested follow-up data for up to week 52 for patients who demonstrated a more than 50% decrease in semen parameters by week 26 and failed to recover.
To address these concerns, Gilead has been conducting the MANTA study, a safety trial examining male reproductive safety of filgotinib in men with moderate-to-severe inflammatory bowel disease, and the MANTA-RAy study, examining semen parameters of the drug in men with active RA, psoriatic arthritis, ankylosing spondylitis and nonradiographic axial spondyloarthritis.
Topline results from these studies will be available by mid-2021, when Gilead is expected to refile with the FDA.
However, the initial rejection from the FDA appears to have shaken Gilead’s confidence in the drug, with the company announcing in December that it no longer plans to pursue approval for filgotinib in the U.S.
In a release, Gilead noted that the 200 mg dose “is required to be competitive in RA in the United States and that [this] dose is unlikely to achieve approval for RA in the U.S. without conducting substantial additional clinical studies.” With tight competition from other janus kinase inhibitors — upadacitinib (Rinvoq, AbbVie), tofacitinib (Xeljanz, Pfizer) and baricitinib (Olumiant, Eli Lilly & Co.) — an underpowered 100 mg dose of filgotinib faces an increasingly difficult U.S. market.
Although Gilead has scrapped its RA trials, filgotinib clinical trials will continue for patients with IBD where the company believes “the competitive landscape and FDA considerations may be different” compared with rheumatic conditions. This less competitive indication, combined with pending results from MANTA/MANTA-RAy and a growing list of approvals from other countries, may provide a toehold for filgotinib to return to the RA arena in the U.S.
“We are delighted with the NICE recommendation for Jyseleca,” Onno van de Stolpe, chief executive officer of Galapagos, said in the release. “For patients with moderate-to-severe RA in England, this decision represents a significant new opportunity and especially for those with moderate symptoms who can now receive an advanced treatment earlier.”