Gilead Eyes 2019 FDA Submission for Filgotinib

Filgotinib’s portfolio is expanding.

The investigative Janus kinase (JAK1) inhibitor from Gilead Sciences has been accepted for marketing review by the European Medicines Agency (EMA) as a potential therapy for rheumatoid arthritis.

With European Union consideration pending, Gilead is now planning to submit a New Drug Application (NDA) to the US Food and Drug Administration (FDA) by the end of 2019.

The benefit of filgotinib in patients with moderate to severe rheumatoid arthritis was recently evidenced in the 24-week, phase 3 FINCH 2 trial—a study which compared 200 mg or 100 mg filgotinib versus placebo in 448 patients with arthritis.

The multinational, randomized trial ran from July 2016 to June 2018 across 114 sites. All recruited patients had previously reported an inadequate response or intolerance to 1 or more biologic disease-modifying antirheumatic drugs (DMARDs).

Investigators treated 153 patients with 100 mg filgotinib, 148 patients with 200 mg, and 148 with placebo. Patients also continued concomitant stable conventional synthetic DMARDs during treatment. Mean patient age was 56 years, with 80.4% being women, and 23.4% having been treated with at least 3 biologic DMARDs.

The team assessed for a primary endpoint of proportion of patients to achieve 20% improvement in American College of Rheumatology (ACR20) following 12 weeks of care.

At 12 weeks, a greater rate of patients administered either 100 mg (57.5%) or 200 mg (66.0%) filgotinib achieved ACR20 response than those administered placebo (31.1%; P < .001). The difference in ACR20 response was similar across treated and untreated patients with exposure to at least 3 biologic DMARDs (P < .001).

Common adverse events included nasopharyngitis, headache, and upper respiratory infection for either dosage of filgotinib.

Though the results were positive and the primary endpoint was met, investigators reiterated the need for further long-term efficacy and safety research for the JAK1 inhibitor.

“The 24-week duration precludes conclusions regarding longer-term safety and duration of benefit,” they noted. That said, the extension FINCH 4 trial is seeking long-term outcomes for patients to have previously participated in the study program.

The cause of rheumatoid arthritis is not yet a fully understood concept, investigators noted—several cytokine pathways, among other factors, have been associated with its pathogenesis. The benefit of JAK inhibitor therapy comes from their signal-blocking capability across multiple cytokines, growth factors, and hormones involved with autoimmune disease.

“JAK inhibition may, therefore, have potential as a therapeutic option for a range of inflammatory conditions including RA,” they wrote.

How filgotinib's presence on either the European or US market—or both&mdash;influences rheumatoid arthritis care options will be decided by regulatory authorities in the near future.