Gilead Sciences and Galapagos reported that two Phase III studies of the experimental drug filgotinib in adults with moderately-to-severely active rheumatoid arthritis met their primary endpoints, while a pooled analysis also supported the safety of the oral, selective JAK1 inhibitor. John McHutchison, head of R&D at Gilead, said "the data continue to support filgotinib's potential as a JAK1 specific inhibitor that may provide clinically meaningful responses combined with a favourable safety profile in a wide range of people living with rheumatoid arthritis." Shares in Galapagos rose nearly 16 percent on the news.
Specifically, the FINCH 1 trial examined the safety and efficacy of filgotinib, at a dose of 100 mg or 200 mg, in comparison with AbbVie's Humira (adalimumab) or placebo in 1759 adults with moderately-to-severely active rheumatoid arthritis who have an inadequate response to methotrexate. All treatments were administered in combination with methotrexate, with the study's primary endpoint being the American College of Rheumatology 20 percent response (ACR20) after 12 weeks, while secondary goals included ACR50, ACR70 and clinical remission.
Meanwhile, the FINCH 3 trial assessed filgotinib, at a dose of 100 mg or 200 mg, in combination with methotrexate, or as monotherapy at the high dose, in 1252 methotrexate-naïve adults with moderately-to-severely active rheumatoid arthritis. The study's primary endpoint was ACR20 at week 24, while rates of ACR50, ACR70 and clinical remission were also measured.
Data from the FINCH 1 trial showed that 76.6 percent of patients who received filgotinib 200 mg achieved ACR20 at week 12, while for the lower dose of the drug, the rate was 69.8 percent, with both significantly greater than the rate of 49.9 percent seen in the placebo group. Regarding secondary endpoints, the ACR50 rates in the low- and high-dose filgotinib groups were 36.3 percent and 47.2 percent, respectively, versus 19.8 percent for placebo.
Gilead and Galapagos added that the low- and high-doses of filgotinib were associated with ACR70 rates of 18.5 percent and 26.3 percent, respectively, compared with 6.7 percent for placebo, while the clinical remission rates in the 100-mg and 200-mg dose filgotinib arms were 23.8 percent and 33.9 percent, respectively, versus 9.3 percent in the placebo group. The companies also noted that filgotinib 200 mg displayed superiority to Humira on clinical remission as measured using the DAS28 score, with rates of 33.9 percent and 23.7 percent, respectively.
Meanwhile, results from the FINCH 3 study showed that 81 percent and 80.2 percent, respectively, of patients who received filgotinib at doses of 200 mg and 100 mg in combination with methotrexate achieved ACR20 at week 24, which were both significantly higher than the rate of 71.4 percent seen in the placebo group. Gilead and Galapagos added that the ACR50 rates in the low- and high-dose filgotinib combination groups were 57 percent and 61.5 percent, respectively, compared with 45.7 percent for placebo.
Additionally, the ACR70 rates in the low-and high-dose combination groups were 40.1 percent and 43.8 percent, respectively, versus 26 percent for placebo. Regarding clinical remission, the rates in the low- and high-dose filgotinib combination groups were 42.5 percent and 54.1 percent, respectively, compared with 29.1 percent for placebo.
The drugmakers said that results from both studies will be presented at a future research meeting. The news comes after Gilead and Galapagos unveiled data from the late-stage FINCH 2 study last September illustrating that filgotinib was associated with higher response rates than placebo in patients with moderately-to-severely active rheumatoid arthritis who had an inadequate response or intolerance to prior biologic agents.
Commenting on the news, KBC Securities analysts stated that the main takeaway is that filgotinib is likely to win approval in the US, EU and Japan, raising the probability of approval from 75 percent to 90 percent. The analysts additionally cited the superior safety profile of filgotinib at higher doses versus comparators. A pooled analysis of the three FINCH studies found that there were four deaths in patients receiving filgotinib, compared to two in the placebo arm. Meanwhile, major adverse cardiac events occurred in five subjects given filgotinib versus five on placebo, and deep venous thrombosis/pulmonary embolism was seen in only one patient administered the experimental drug, compared to three for placebo.
Gilead and Galapagos are jointly developing filgotinib under a 2015 agreement potentially worth more than $2 billion. Galapagos had previously regained full rights to the therapy after AbbVie declined an option to in-license the drug.
For further analysis, read ViewPoints: Gilead's filgotinib breaks the JAK inhibitor safety trend.
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