Gilead received a big shock following the FDA’s complete response letter (CRL) for filgotinib. While there has always been concerns surrounding the Janus kinase (JAK) inhibitor’s safety class profile across the immune space, Gilead’s hopes to differentiate the drug as ‘the safest JAK’ due to its lower rate of adverse events from cross-trial comparisons is now dashed by the CRL, which triggered stocks to fall by 5% (28% for partner Galapagos). Experts interviewed by GlobalData have long called for head-to-head studies within the class, and this may be just the strategy that filgotinib needs to quell concerns and bring it back to the lead in terms of safety in minds of stakeholders.

Heather Leach, PhD, Director of Immunology at GlobalData, comments: “While a head-to-head trial would be a risky gamble, competitors are making headway over filgotinib; with billions of dollars on the line, it may well be a risk worth taking.”

JAK inhibitors have had a checkered past with regulators, and the FDA has issued a black box warning on all three approved agents in rheumatoid arthritis (RA) – Pfizer’s Xeljanz, Eli Lilly’s Olumiant, and AbbVie’s Rinvoq – for the risk of serious infections, tuberculosis, lymphoma, and thrombosis. The FDA’s feedback on the higher 200mg dose of filgotinib was not necessarily a surprise, as this has come up before with the US agency in 2012 for Xeljanz during its FDA regulatory review and again in 2018 for Olumiant, when only the low-dose was approved after an initial rejection of the drug.

Leach continues: “While the news of the CRL shocked stakeholders across the industry, the biggest loss was for Gilead and Galapagos with significant impact to filgotinib’s anticipated arrival to the RA market, potentially dashing hopes that safety would be a differentiating factor and key to becoming best-in-class. GlobalData now assumes that filgotinib’s earliest launch in the US will be H1 2022, rather than the initial expectation of Q3 2020.”

For more information, send your questions to Rebecca Panks, PR Executive at GlobalData (pr@globaldata.com)