Gilead Sciences and Galapagos announced Week 24 results of the ongoing FINCH 1 and FINCH trials evaluating filgotinib in adults with moderately-to-severely active rheumatoid arthritis. Both trials have met the primary endpoint of American College of Rheumatology 20 percent response (ACR20) rate, defined as a greater than 20% improvement in tender or swollen joint counts; with response rates greater than or similar to adalimumab (Humira) and methotrexate. The safety profile was similar across treatment arms and compared to placebo.
FINCH 1 is a 52-week randomized, double-blind, placebo- and active-controlled study, enrolling 1,759 adult patients with moderately to severely active RA who have an inadequate response to methotrexate (MTX). Eligible patients were randomized (3:3:2:3) to receive filgotinib 200 mg (n=477), filgotinib 100 mg (n=480), adalimumab (Humira) (n=325) or placebo (n=477) in addition to a stable dose of MTX. The primary endpoint of the study is the proportion of patients who achieve an American College of Rheumatology 20 percent improvement response (ACR20) at Week 12. The ACR20 response rate for each treatment arm is as follows (% of patients responding): filgotinib 200 mg + MTX: (76.6%); filgotinib 100 mg + MTX: (69.8%); adalimumab + MTX: (70.8%) and placebo + MTX (49.9%). The proportion of patients achieving ACR50 and ACR70 response was also significantly greater for filgotinib compared with placebo at Week 12, for both doses. In addition, when compared to placebo at week 12, both doses of filgotinib resulted in a statistically significant reduction in the Health Assessment Questionnaire Disability Index (HAQ-DI) and led to a significantly higher proportion of patients achieving clinical remission (DAS28(CRP) < 2.6) and low disease activity (DAS28(CRP) < 3.2). When comparing low disease activity rates at Week 12, filgotinib 200 mg was non-inferior to adalimumab. Filgotinib 100 mg and 200 mg also significantly inhibited the progression of structural damage at Week 24. Source
FINCH 3 is an ongoing 52-week randomized, double-blind and active-controlled study examining filgotinib alone and in combination with MTX, enrolling 1,252 adult patients with moderately to severely active RA who are naïve to MTX. Patients were randomized (2:1:1:2) to receive filgotinib 200 mg plus MTX (n=417), filgotinib 100 mg plus MTX (n=207), filgotinib 200 mg alone (n=210) or MTX (n=418). The primary endpoint is the proportion of patients who achieve an ACR20 response at Week 24. The ACR20 response rate for each treatment arm is as follows (% of patients responding): filgotinib 200 mg plus MTX: (81%); filgotinib 100 mg plus MTX: (80.2%); filgotinib 200 mg alone: (78.1%) and MTX (71.4%). The proportion of patients achieving ACR50, ACR70, and clinical remission (DAS28(CRP) < 2.6) at Week 24 was also significantly higher for patients receiving once-daily filgotinib 100 mg or 200 mg plus MTX compared with patients receiving MTX alone. Additionally, those who received filgotinib experienced greater reduction in the HAQ-DI compared with those receiving MTX alone at Week 24. Filgotinib 200 mg monotherapy inhibited the progression of structural damage at Week 24 compared with MTX alone as assessed by modified total Sharp score (mTSS). source
In both trials the rate of serious adverse events, including serious infections, was low and balanced across the treatment arms. There was one venous thrombotic event (in the MTX group), five cases of adjudicated major adverse cardiovascular events (two in the filgotinib 200 mg plus MTX group, one in the filgotinib 200 mg group and two in the MTX group) and one malignancy (in the MTX group). There was one death, reported in the filgotinib 200 mg plus MTX group.
Filgotinib is a selective JAK1 (Janus kinase 1) inhibitor. JAK1 is an enzyme with an essential role in the promotion of biologic responses induced by a subset of cytokine receptors, proteins that lead to inflammation.
Gilead entered into a worldwide agreement with Galapagos NV in December of 2015 for the development and commercialization of filgotinib for inflammatory disease indications.