A phase 3 trial of Gilead and Galapagos’ JAK1 inhibitor filgotinib in rheumatoid arthritis has met its primary endpoint. The data suggest filgotinib is safe and as effective as JAK rivals including AbbVie’s upadacitinib, setting the stage for a four-way commercial scrap.

Gilead bought its way into the JAK1 field when it paid Galapagos $725 million for rights to filgotinib. Since then, the pair has embarked on a multifront clinical campaign designed to establish filgotinib as a credible rival to JAK inhibitors from Pfizer, Eli Lilly and AbbVie. Pfizer’s Xeljanz and Lilly’s Incyte-partnered Olumiant are on the market but have been dogged by safety issues. AbbVie’s JAK inhibitor is still in development but has a comfortable developmental lead over filgotinib.

The competitive situation means Gilead and Galapagos need to generate excellent safety and efficacy data to have a shot at turning filgotinib into the big blockbuster analysts are anticipating. That has made the FINCH 2 readout a key early test of filgotinib’s prospects. While there is a long way to go and many questions remain unanswered, the results mean filgotinib is still in the game.

In the higher-dose arm, 66% of participants achieved a 20% or greater improvement in symptoms assessed by the ACR20 scale after 12 weeks, resulting in the trial hitting its primary endpoint and filgotinib chalking up a placebo-adjusted benefit of 34.9%. The placebo-adjusted figures for the measures of 50% and 70% symptom improvements were 28% and 15%, respectively. Filgotinib beat placebo by similar margins at the subsequent 24-week readout. Remission results were positive, too.

The placebo-adjusted figures are in line with those generated in late-phase trials of rival JAK drugs, suggesting filgotinib can hold its own in terms of efficacy. If that proves to be the case—something far from certain given the difficulties of trial-to-trial comparisons—safety will emerge as a key battleground for filgotinib and its rivals.

Filgotinib came through FINCH 2 without sounding any safety alarms. Importantly, there were no reports of deep vein thrombosis or pulmonary embolism, safety concerns linked to Olumiant and Xeljanz.

The clean safety profile and solid efficacy data generated in FINCH 2 leave filgotinib with a few more hurdles to clear. Gilead and Galapagos are working to wrap up two other phase 3 trials that will yield more safety and efficacy data. In parallel, the partners are racing to clear up the one safety area in which filgotinib may have a disadvantage: testicular toxicity. 

At one point, a potential link between filgotinib and testicular toxicity raised fears that regulators would bar Gilead and Galapagos from trialing a 200 mg dose. Those fears proved to be unfounded, but Gilead and Galapagos included a dedicated male patient testicular safety study in the late-phase program to further probe the link. That study is still enrolling patients. A note from Jefferies analyst Michael Yee stated Gilead "is working hard to accelerate enrollment which may include opening it up to other indications and lots more sites."

Shares in Gilead rose close to 3% after hours. Galapagos jumped 16% in early trading in Amsterdam.

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