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A drug for rheumatoid arthritis that was seen as potentially a significant driver of growth has been turned down by the Food and Drug Administration, dealing a blow to the companies that developed it.

Foster City, California-based Gilead Sciences said in an after-hours announcement Tuesday that it had received a complete response letter from the FDA for filgotinib for moderately to severely active rheumatoid arthritis. Gilead has been developing filgotinib under a collaboration with Belgian biotech company Galapagos.

Shares of Gilead were down nearly 4% on the Nasdaq in mid-morning trading Wednesday. The news was even worse for Galapagos, whose shares were down 24% on the Amsterdam Exchange. The companies signed a more than $5 billion deal to develop the drug in July 2019.

In the letter, the FDA requested data from the two of the studies the companies used for approval, MANTA and MANTA-RAy, before completing its review of the companies’ application. It also expressed concerns about the overall risk-benefit profile of filgotinib when administered at the 200mg dose level. Both studies are fully recruited, and topline results are expected in the first half of next year.

“We are disappointed in this outcome and will evaluate the points raised in the CRL for discussion with the FDA,” said Merdad Parsey, Gilead’s chief medical officer, in a statement. “We continue to believe in the benefit-risk profile of filgotinib in RA, which has been demonstrated in the FINCH Phase III clinical program.”

To be sure, the companies’ pursuit of filgotinib’s approval was not seen as risk-free. In June of this year, RBC Capital Markets analyst Brian Abrahams wrote in response to the announcement of positive follow-up data from two of the FINCH studies that although there was a good likelihood of the drug receiving a green light from the FDA, potential safety risks – even if seemingly minor – could potentially derail approval, particularly at the 200mg dose.

Nevertheless, Morgan Stanley analyst Matthew Harrison called the FDA’s decision a surprise, noting that the drug had received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use. Citing a discussion with the companies, he wrote that while the companies have provided the FDA with blinded interim data from the MANTA studies, the FDA indicated it needed the complete, unblinded data. Meanwhile, the issue with the 200mg dose was characterized as being related to the overall safety profile versus the 100mg dose, but that agency was not focused on a particular safety imbalance, and there was not any surprise safety event in the database.

The CRL delays filgotinib’s launch by at least one year – 12-18 months in a best-case scenario – wrote Cowen analyst Phil Nadeau, adding that his firm had been optimistic, particularly after the CHMP’s positive opinion. He noted that it was FDA concerns about testicular toxicity with the drug’s 200mg dose that led to the MANTA studies, though the FDA did not specify issues with the risk-benefit of the 100mg dose, and eventual approval seems likely.

“Unfortunately, the CRL implies there is risk that filgotinib’s 200mg dose will not be approved for RA in the U.S. which would diminish GILD/GLPG’s competitive position,” Nadeau wrote.

“Gilead’s CRL for filgotinib in RA comes as quite a surprise, given the confidence the team has had in this asset and a pathway for it through regulatory,” wrote another analyst, Baird’s Brian Skorney. “Although the testicular [toxicity] has been a background concern, the language around questions on the overall benefit/risk profile for the 200mg dose is of concern and could impact the commercial opportunity relative to AbbVie’s Rinvoq and other RA therapies.”

Photo: FDA (via Flickr; free of copyright protection)



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