Gilead has paused enrollment in clinical trials of filgotinib in three indications pending feedback from the FDA. The cessation of enrollment follows the FDA’s decision to reject a filing for approval of the JAK1 inhibitor in rheumatoid arthritis due to toxicity concerns.
In the fourth quarter, Gilead will meet with the FDA to discuss the complete response letter (CRL). Talking to investors late on Wednesday, Gilead Chief Medical Officer Merdad Parsey, M.D., Ph.D., said enrollment in trials of psoriatic arthritis, ankylosing spondylitis and uveitis patients has stopped. Gilead took the action in the belief the FDA meeting will inform the broader filgotinib development program.
Working with its partner Galapagos, Gilead began a phase 2 trial in uveitis in 2017, before going on to initiate two phase 3 trials in patients with active psoriatic arthritis in 2019. Gilead changed the status of all three trials to “active, not recruiting” in recent days.
Gilead only filed to run the two phase 3 trials in ankylosing spondylitis in July. Neither of the trials has started enrollment and now will not do so until after Gilead has received feedback from the FDA.
The feedback could have major implications for filgotinib, a drug widely tipped to be a blockbuster before the FDA rejected Gilead’s application. Asked whether the FDA’s feedback could persuade Gilead to abandon plans to launch in the U.S., Parsey said “the options you suggested are possible.” Currently, Parsey would “tend toward” a more nuanced approach that sees filgotinib launch in inflammatory bowel disease even if the rheumatoid arthritis opportunity is blocked by the FDA.
Gilead’s path forward will be dictated by what evidence the FDA wants to see. In disclosing the CRL, Gilead said the FDA had requested data from two clinical trials, MANTA and MANTA-RAy, that are assessing the effect of the 200-mg dose on sperm concentrations and “expressed concerns regarding the overall benefit/risk profile of the filgotinib 200-mg dose.”
The two safety clinical trials are due to deliver data in the first half of next year, although there are suggestions they may fail to fully address FDA’s concerns. At the time of the CRL, analysts at Jefferies said they “understand [the FDA’s concern] does not just relate to male toxicity.”
The concern about the effect of the 200-mg dose on sperm began when toxicology data in rats and dogs led Galapagos to only use the 100-mg dose at U.S. sites in a phase 2 trial. Gilead and Galapagos went on to study 200 mg in phase 3 but are yet to allay the concerns of the FDA. Most of the studies paused by Gilead feature 100-mg and 200-mg cohorts. The one exception is the uveitis trial, which is only testing filgotinib at the higher dose.
Regulatory resistance to the use of filgotinib at 200 mg could kill off hopes of selling the drug in the U.S. in some indications, particularly given delays to gather additional data will further strengthen the position of AbbVie’s rival JAK1 inhibitor Rinvoq.