Filgotinib Safe, Effective in Treating Ankylosing Spondylitis, Phase 2 Trial Shows

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by Marta Figueiredo |

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Filgotinib, an investigational therapy for ankylosing spondylitis (AS) and other inflammatory diseases, was able to significantly reduce disease activity, according to recent Phase 2 clinical trial results announced by Gilead Sciences and Galapagos biotech companies.

The trial’s findings, “Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial,” were published in the The Lancet.

AS patients have an overproduction of cytokines — small proteins that act as chemical messengers between cells of the immune system — resulting in a higher-than-normal recruitment of immune cells to the joints of the spine, which causes damaging inflammation.

Filgotinib, discovered and developed by Galapagos, is an oral treatment that selectively targets and suppresses the activity of Janus kinase 1 (JAK1), a protein essential for the transmission of cytokine-associated chemical messages.

This way, filgotinib blocks cytokine-dependent inflammatory responses, reducing inflammation and the potential for permanent damage.

In December 2015, Galapagos and Gilead Sciences entered into a global collaboration for the development and commercialization of filgotinib in inflammatory diseases, including AS and psoriatic arthritis.

The randomized, placebo-controlled, Phase 2 trial (NCT03117270), known as TORTUGA, evaluated the safety and effectiveness of filgotinib in 116 adults with moderately-to-severely-active AS who were not responding to standard treatments.

This proof-of-concept trial was conducted at 30 sites in Belgium, Bulgaria, the Czech Republic, Estonia, Poland, Spain, and Ukraine.

Patients were randomized to receive once daily either 200 mg of filgotinib (58 patients) or a placebo (58 patients), for 12 weeks. Among them, 55 (95%) patients in the filgotinib group and 52 (90%) in the placebo group completed the study.

The trial’s primary objective was to assess reductions in patients’ disease activity through the ankylosing spondylitis disease activity score (ASDAS), a validated measure of disease activity based on the scores of five domains: back pain, joint pain and/or swelling, morning stiffness, global assessment of disease activity, and levels of C-reactive protein (a blood marker of inflammation).

Secondary goals included determining the proportion of patients who achieved at least a 20% (ASAS20) or 40% (ASAS40) improvement in at least three of the four main domains of Assessment of Spondyloarthritis international Society (ASAS) — physical function, pain, patient global assessment, and inflammation — and patients’ quality of life – assessed through Ankylosing Spondylitis Quality of Life questionnaire (ASQoL).

Results showed that reductions in disease activity were significantly greater in the filgotinib group, compared with the placebo group, from the first week of treatment.

After 12 weeks of treatment, patients who received filgotinib showed a significantly greater decrease in the disease activity score (1.5 reduction) than patients in the placebo group (0.6 reduction).

Roughly 66% of patients in the filgotinib group had a clinically significant reduction in disease activity, compared with 26% of patients in the placebo group.

A significantly greater proportion of patients receiving filgotinib also achieved ASAS20 (76%) and ASAS40 (38%) responses, compared to those treated with a placebo (40% and 29% of them met ASAS20 and ASAS40 responses, respectively).

Filgotinib also was found to significantly improve patients’ quality of life, compared to placebo.

The therapy was well-tolerated, with most adverse side effects being mild to moderate in severity, and the compound’s safety profile was consistent with that reported in previous clinical trials. In each group, 18 patients (31%) had treatment-related adverse side effects and one patient (1.7%) stopped treatment because of it.

No unexpected safety signals were observed, and there were no deaths, malignancies, liver events, opportunistic infections, gastrointestinal perforations, or cases of shingles.

Researchers noted that while the data highlight filgotinib as an effective therapy to treat patients with AS who do not have adequate responses to standard first-line therapy, larger and longer-term clinical studies are required to confirm these results.

Results of the Phase 2 EQUATOR study (NCT03101670), which evaluated the safety and effectiveness of filgotinib in 131 patients with moderately-to-severely-active psoriatic arthritis, also were published in the same journal, under the title “Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial.”

The promising results showed that filgotinib safely and effectively eased signs and symptoms of psoriatic arthritis in patients who did not respond to standard therapies.

“We are pleased that filgotinib demonstrates a consistent safety and efficacy profile across multiple inflammatory conditions, including psoriatic arthritis and ankylosing spondylitis,” Walid Abi-Saab, MD, Galapagos’ chief medical officer, said in a press release.

“We look forward to sharing additional updates as we continue to develop this compound for patients in need of additional therapy options,” he added.