Gilead Suspends Enrollment in Phase 3 Trials of Filgotinib in AS

Gilead Sciences has suspended enrollment in two Phase 3 trials studying the effects of filgotinib, an anti-inflammatory therapy currently being investigated in several inflammatory conditions, in patients with ankylosing spondylitis (AS).

The trials, SEALION2-NAÏVE (NCT04483700) and SEALION1-IR (NCT04483687), set out to determine if filgotinib is potentially superior to a placebo at increasing the proportion of patients with active AS achieving a minimum of 40% improvement in three of four domains — patient global assessment of disease, pain, function, and inflammation — in the Assessment in SpondyloArthritis International Society response criteria after 16 weeks of treatment.

While SEALION2-NAÏVE aims to enroll 408 participants who had never been treated with a biological disease-modifying anti-rheumatic drug, SEALION1-IR expects to recruit 576 who previously received but failed to respond adequately to such therapies.

Patients enrolled in both studies will have the option to join a long-term extension study after completing 16 weeks of treatment with either filgotinib tablets (100 or 200 mg) or a placebo in the main trial. The extension study, where all patients will receive either 100 or 200 mg of filgotinib once daily, will last up to 1.5 years.

In addition to these trials, Gilead also suspended other ongoing studies that were assessing the effectiveness of filgotinib in people with psoriatic arthritis and uveitis, an inflammatory disease that causes swelling and damages eye tissues.

The decision to halt enrollment in these studies was announced by the company in a recent conference call. According to Gilead, the decision was motivated by a complete response letter issued by the U.S. Food and Drug Administration (FDA) in August in response to an application requesting filgotinib’s approval for rheumatoid arthritis.

In the letter, the FDA expressed concerns about the benefit-risk profile of the medication — specifically when administered at a dose of 200 mg — and requested data from two Phase 2 trials assessing filgotinib’s effect on sperm concentration, MANTA (NCT03201445) and MANTA-RAy (NCT03926195), before completing its review. Top-line data from both studies are expected in the first half of 2021.

“We met with the FDA for a Type C meeting to discuss MANTA, and we’ll meet again for a Type A meeting [later this year] to further discuss the CRL [complete response letter],” Merdad Parsey, MD, PhD, chief medical officer of Gilead, said during the company’s conference call.

“In the meantime, we’re pausing screening and enrollment for ongoing trials in psoriatic arthritis, ankylosing spondylitis and uveitis as we believe the FDA meeting will inform the broader filgotinib development program,” he added. “We continue to believe in the benefit/risk profile of filgotinib.”

Filgotinib is an oral inhibitor of Janus kinase 1 (JAK1) that is being jointly developed and commercialized by Galapagos and Gilead. JAK1 is a protein that plays a key role in transmitting chemical signals in cells, especially those linked to inflammation. By blocking JAK1, filgotinib is expected to lower the activation of signaling cascades inside cells that promote inflammation, as well as the signs and symptoms of multiple inflammatory diseases, including AS.

In Europe, the medication was recently approved — under the brand name Jyseleca — for the treatment of adults with moderately to severely active rheumatoid arthritis, who failed to respond or are intolerant to one or more disease-modifying anti-rheumatic drugs. The approval includes 100 and 200 mg tablets, which can be taken as a stand-alone therapy, or used in combination with methotrexate, a medication sometimes prescribed to treat those with severe rheumatoid arthritis.

Gilead and Galapagos recently announced new data from a Phase 2/3 trial, called SELECTION (NCT02914522), which demonstrated that when given once daily at a dose of 200 mg, filgotinib safely enabled patients with moderately to severely active ulcerative colitis, a form of inflammatory bowel disease, to achieve clinical remission within 10 weeks and remain symptom-free up to week 58.

Importantly, the proportions of patients achieving sustained remission and taking no corticosteroids for at least six months were higher with filgotinib than with a placebo.

Based on these findings, Parsey said the companies are planning to submit an application requesting the approval of filgotinib for ulcerative colitis in Europe before the end of the year, and in Japan in early 2021.