A phase 2 trial of Gilead and Galapagos’ filgotinib in psoriatic arthritis has met its primary endpoint. The midphase trial linked the JAK1 inhibitor to significant improvements on a symptom score, laying the groundwork for psoriatic arthritis to join the partners’ growing pot of late-phase opportunities.
Investigators enrolled 131 patients who had been failed by conventional disease-modifying therapies, such as methotrexate and sulfasalazine, and randomized them to take filgotinib or placebo once a day. After 16 weeks, 80% of participants in the treatment arm experienced a 20% or greater improvement in their symptoms (ACR20), compared with 33% of people in the control group.
The finding resulted in the study hitting its primary endpoint. Gilead and Galapagos also reported statistically significant differences in the proportion of patients who experienced 50% and 70% improvements in their symptoms.
Importantly, the data suggest filgotinib can hold its own against approved treatments of psoriatic arthritis. AbbVie’s Humira won approval in the indication on the strength of data linking it to a 44% placebo-adjusted improvement in the proportion of patients achieving ACR20 after 12 weeks. The filgotinib phase 2 reported a 47% improvement after 16 weeks. The figures for ACR50 and ACR70 are similarly comparable. Both drugs performed better than Pfizer’s approved JAK inhibitor Xeljanz.
The limitations of cross-trial comparisons mean it is impossible to draw firm conclusions from these data. And the presence of rivals such as AbbVie’s upadacitinib and Eli Lilly and Incyte’s baricitinib in late-phase pipelines means the competitive landscape could look different by the time filgotinib gets approved in the indication. That said, the available data suggest filgotinib could be competitive.
Filgotinib will need solid efficacy data to compete, but safety issues could dictate which drugs win out. The JAK class is linked to serious infections, an issue that led the EMA to reject Xeljanz in 2013. And thromboembolic events have caused Lilly and Incyte’s baricitinib regulatory problems.
Safety data from the phase 2 filgotinib trial were in line with signals seen in earlier studies of the drug. One patient in the filgotinib arm suffered a serious infection and died and another developed herpes zoster.
The events suggest filgotinib suffers from some of the class-wide issues, but the lack of any cases of opportunistic infection, tuberculosis, thromboembolism or malignancy is in its favor. Gilead and AbbVie think their JAK drugs may be free from the thrombosis issue that has blighted baricitinib.
Gilead and Galapagos disclosed the top-line data alongside news that filgotinib has cleared a phase 2b futility analysis in ulcerative colitis. The success clears both the 100 mg and 200 mg doses of filgotinib to move into phase 3 in the indication, triggering a $15 million payment from Gilead to Galapagos.
The clearing of the futility analysis was expected but is an incremental positive given filgotinib advanced into the phase 2b on the back of data in Crohn’s disease, not ulcerative colitis, and earlier comments by Gilead.
“While there will be some debate as to how much anyone can read into an interim futility to proceed, comments from Gilead have suggested that the hurdle for go/no-go was sufficient to meet enough efficacy signs to merit the investment and go-forward decision which is good,” Jefferies analyst Michael Yee wrote in a note to investors.