Gilead's filgotinib phase 3 hits primary endpoint but details dampen hopes

A phase 2b/3 trial of Gilead Sciences and Galapagos’ filgotinib in ulcerative colitis patients has met its primary endpoint. Yet, with the lower dose missing a key endpoint, investors responded negatively to the data, sending shares in Galapagos down 7% in early trading in Amsterdam.

Gilead and Galapagos are looking to JAK1 inhibitor filgotinib to rack up blockbuster revenues across a clutch of indications despite the presence of direct competitors such as AbbVie’s Rinvoq. Filgotinib is under review at regulatory agencies around the world in the treatment of rheumatoid arthritis. The data shared after the market closed Wednesday are key to the effort to expand into adults with moderately to severely active ulcerative colitis.

The top-line results featured elements to encourage both bulls and bears. Gilead focused on the success of the 200-mg dose at improving the induction and maintenance of remission in patients, regardless of whether they had previously taken biologics. The safety data shared so far are also free from red flags, adding to hopes that can be a point of differentiation for filgotinib.

Jefferies analysts called the efficacy seen in patients who received 200 mg of filgotinib “compelling,” adding that they underpin hopes the drug will be a blockbuster. The analysts tip sales of filgotinib to top out at $6 billion, around $400 million of which is expected to come from use in ulcerative colitis.

However, as the Jefferies analysts acknowledge, there are aspects of the top-line data that are less impressive. Perhaps most notably, the 100-mg dose failed to outperform placebo in terms of inducing remission over the first 10 weeks of the trial. All three doses of Rinvoq hit the induction endpoint in a phase 2b ulcerative colitis trial run by AbbVie. 

The weaker aspects of the data led Cory Kasimov and his colleagues at JPMorgan to say the results are “not exactly the filgood moment” they were expecting. Exactly how good or bad the data are will start to become clearer when Gilead and Galapagos share a fuller look at the results.

Based on the available data, the 200-mg dose of filgotinib looks like it may be able to hold its own in a head-to-head against Rinvoq, although the relatively high placebo rate seen in the Gilead trial makes the already fraught task of comparing data from across clinical trials harder still. 

“Ultimately, we find this hard to compare to other JAK inhibitors in the class and will look to full data to better understand how/if filgo’s clinical profile is differentiated,” Kasimov and his colleagues wrote in a note to investors.

In the absence of home run efficacy data, Gilead and Galapagos may try to look to safety to set their drug apart from the pack. The top-line data are free from red flags that could undermine that strategy but equally lack key information such as the rates of deep venous thrombosis and pulmonary embolism.