The FDA has rejected the submission of Gilead for approval of filgotinib in rheumatoid arthritis. With the FDA requesting to see data from an ongoing clinical trial, Gilead is unlikely to be able to refill until after the middle of next year, pushing it even further behind its rivals for the JAK inhibitor market.
In disclosing the full response letter, Gilead said the FDA has requested data from two ongoing clinical studies, MANTA and MANTA-RAy, which assess the effect of the 200-mg dose of JAK1 inhibitor filgotinib on sperm concentrations . The FDA has also “expressed concerns about the overall benefit / risk profile of the filgotinib 200 mg dose,” according to Gilead.
Gilead said MANTA and MANTA-RAy are fully enrolled and are expected to provide data in the first half of next year. The need to wait for test results before refilling suggests that it may be mid-2021 before Gilead returns to the FDA. That timeline implies an early approval of 2022, should the FDA win green light.
The delay is a significant commitment for a drug that analysts at Jefferies are tipping to generate $ 3 billion in annual sales in rheumatoid arthritis and the same recurrence in other indications. That prognosis was already questioned by doubts about Gilead’s ability to take part in AbbVie, which won approval for its JAK1 drug Rinvoq a year ago. Rinvoq generated $ 149 million in the second quarter.
Gilead and filgotinib partner Galapagos have framed safety as a positive differentiator for filgotinib over other JAK1 inhibitors, all of which have so far all come with a warning of black boxes. However, the effect of the drug on sperm is a long-standing concern.
Analysts speculate that concerns about testicular toxicity may have contributed to AbbVie’s decision to drop filgotinib in 2015 and focus on Rinvoq. Five years later, AbbVie’s decision seems set to pay off.
Concerns about sperm toxicity have been repeated in toxicology studies of the 200-mg dose in rats and dogs. The results, and the FDA’s response to them, led Galapagos to limit the maximum daily dose on US sites in its Phase 2 DARWIN clinical trial to 100 mg. Gilead and Galapagos were later given the green light to enroll a 200 mg cohort in their Phase 3 program.
To allay toxicity concerns, the Galapagos conducted further preclinical tests, enrolled controlled men enrolled in their clinical trials, and, with Gilead, initiated the MANTA and MANTA-RAy studies. The work and talks with the FDA led Gilead and the Galapagos to think that they could seek approval without data from MANTA and MANTA-RAy.
“Neither is required to … gate-submit,” Walid Abi-Saab, chief medical officer at Galapagos, told attendees at an R&D event in November. “Once available, they will be used, whether it will be … during the review process or later.”
The FDA has taken a different view. If the toxicity tests are free of red flags, Gilead could be ready to fill out for approval of the 200-mg dose next year. However, that plan could be undermined by the FDA’s “concerns about the overall benefit / risk profile of the filgotinib 200 mg dose.” Analysts at Jefferies said they ‘understand [the FDA’s concern] has not only to do with male toxicity. ”
What this means for the interest of filgotinib and Gilead in it remains unclear. Gilead placed a major bet on the Galapagos last year when it paid $ 5.1 billion to expand its alliance far beyond filgotinib. In a post to discuss the FDA’s rejection, Galapagos CEO Onno van de Stolpe said Gilead continued to “believe in the risk / benefit profile of filgotinib,” adding that he was “convinced that Gilead knew the how and has the experience to determine the next steps, and guide us through this process. ”
However, some analysts question whether Gilead should remain committed to filgotinib. With a series of offers that turned Gilead into oncology, Jefferies analyst Michael Yee raised the question of whether fourth in the class autoimmune drug filgotinib is the best use of the big biotech’s money.
“We believe there is a fair amount of discussion among investors about how much investment GILD should make in filgo – and if they have backed up filgo investments … this would actually be a potential positive for GILD margins and ROI to to invest in other areas, ”Yee wrote in a note to investors.
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