Filgotinib drops out of US arthritis race: Gilead ends bid for FDA approval
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Drug maker Gilead Sciences has announced it will no longer pursue FDA approval for its janus kinase inhibitor filgotinib in the treatment of rheumatoid arthritis, according to a company press release.
The announcement puts an official end to a years-long competition between Gilead and AbbVie, whose upadacitinib (Rinvoq) won the race to enter the drug market as the third JAK inhibitor approved by the FDA for moderate-to-severe RA in 2019.
Gilead had hoped to procure fourth place in the increasingly crowded marketplace — even setting the stage for a potential 2020 launch — until the FDA abruptly rejected filgotinib for RA in August over concerns of testicular toxicity.
Following a meeting with the FDA to discuss that decision, and based on the feedback it received, Gilead said it is now “unlikely” to achieve approval for the drug’s 200 mg formulation for RA without substantial, additional clinical studies.
“While we believe that the clinical profile of Jyseleca could help many patients living with RA, we no longer see a viable path to U.S. approval in this indication,” Daniel O’Day, chairman and chief executive officer of Gilead Sciences, said in a press release.
Troubles stateside
Filgotinib — which is approved under the tradename Jyseleca for RA in Europe and Japan — has been plagued in the United States by lingering concerns regarding its testicular toxicity. 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.
According to Gilead, week 26 data from the MANTA and MANTA-RAy studies, including primary and key secondary endpoints, will be available by mid-2021 and forwarded to regulatory authorities shortly thereafter. To complete its review of filgotinib in RA or other future indications, the FDA has requested follow-up data for up to week 52 for patients who demonstrate a more than 50% decrease in semen parameters by week 26 and fail to recover.
Ending clinical trials for PsA, AS and uveitis
Filgotinib failing to reach the U.S. marketplace for RA is just one piece of the fallout stemming from the FDA’s rejection.
Gilead’s announcement comes as part of a larger shake-up with its European partner Galapagos NV, not only regarding the terms of their business agreement on the development and commercialization of filgotinib, but also the drug’s future in other indications.
Following the FDA’s rejection of filgotinib for RA in August, Gilead and Galapagos paused clinical trials of the drug in PsA, AS and non-infectious uveitis.
Those trials will now permanently cease in the coming months, according to a joint statement from the companies.
“Without a viable path forward in the United States, the companies no longer believe it is feasible to continue the current global development program for filgotinib in these indications,” read the press release.
For Jasvinder Singh, MD, MPH, professor of medicine at the University of Alabama at Birmingham, the news comes as a serious blow to patient choice.
“I think that the decision of Gilead and Galapagos to no longer pursue FDA approval of filgotinib for RA and pause clinical trials of filgotinib in psoriatic arthritis, ankylosing spondylitis and non-infectious uveitis, is a piece of sad news,” Singh told Healio Rheumatology. “If safety concerns from the FDA could be addressed to satisfaction, this medication could have offered an important choice for patients with these diseases.”
Filgotinib clinical trials will continue, however, for patients with IBD, according to the companies. Gilead will retain operational responsibility for ongoing trials in Crohn’s disease while Galapagos will assume the same for the current trials in ulcerative colitis. The drug is current. In their statement, Gilead and Galapagos said they expect to have further clarity on the potential U.S. filing of filgotinib in IBD, after consultation with FDA, including on the results of the MANTA and MANTA-RAy studies.
“Gilead and Galapagos continue to investigate the potential role of filgotinib in UC and Crohn’s disease where this is a significant need for new treatment options, including in the U.S.,” Arran Attridge, a spokesperson for Gilead, told Healio Rheumatology. “Gilead believes the competitive landscape and FDA considerations may be different in IBD than in rheumatic conditions like RA.”
Business shake-ups
On the business side, Gilead and Galapagos announced a raft of changes to the companies’ existing arrangement managing the development and commercialization of filgotinib.
Under the terms of the new arrangement, Galapagos will assume sole responsibility in Europe for filgotinib, in RA, ulcerative colitis and all future indications. In addition, Galapagos will assume responsibility for ongoing RA clinical trials.
Gilead will pay Galapagos 160 million ($195 million) to support ongoing development and accelerated commercial buildout in the European Union. Meanwhile, Gilead will receive royalties on European sales of filgotinib starting in 2024.
“In this new context, Gilead and Galapagos believe it makes sense for Galapagos to drive commercialization in Europe,” O’Day said in the press release. “We are confident that through our strategic alliance with Galapagos, we will deliver many important new therapies for inflammatory diseases in the future.”
Gilead will retain commercial rights, and remain in charge of marketing authorization, for filgotinib outside of Europe, including in Japan, where it is co-marketed with Eisai.
In addition, Galapagos will bear the future development costs for certain studies, in lieu of the equal cost sharing in the companies’ previous agreement. These studies include the DARWIN3, FINCH4, FILOSOPHY, and phase 4 studies and registries in RA, the MANTA and MANTA-Ray studies, the PENGUIN1 and 2 and EQUATOR2 studies in PsA, the SEALION1 and 2 studies in AS, and the HUMBOLDT study in uveitis. Other clinical and non-clinical expenses supporting these studies, as well as support for any investigator sponsored trials in non-IBD conditions and non-clinical costs on all current trials, will also be taken on by Galapagos.
“Jyseleca is already providing an important new treatment option, making a difference to the lives of patients living with RA, where it is available in Europe,” Onno van de Stolpe, chief executive officer of Galapagos, said in the release. “While we are very disappointed by the outcome of the FDA meeting, we are excited that we can now accelerate the plan for Galapagos to lead on commercial activities in Europe in our ongoing collaboration with Gilead, and fully leverage the commercial organization Galapagos has built for the Jyseleca launch. This is an important new chapter in Galapagos’ ongoing journey to be a leading European biotech company in inflammation and fibrosis.”
Perspective
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It's an exciting time for our patients with chronic inflammatory diseases. New therapies are coming to market, and clinical trials are underway all over the world. While we need to continue to pursue options for our patients that are difficult to treat, we need to ensure that drug safety is a priority.
I find it interesting that some medications are approved in other countries but halted in the U.S., or that they are safe for some diagnoses but not others. The FDA’s rejection of the higher dose of filgotinib for use in RA reminds us that the medications we are so used to working with are very potent, and their side effects can be severe.
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