Filgotinib Seen to Reduce AS Disease Activity in Phase 2 Trial, Results Show

Filgotinib, an investigational therapy for ankylosing spondylitis, was able to significantly reduce disease activity, according to recent Phase 2 study results announced by Gilead Sciences and Galapagos biotech companies.

The TORTUGA trial reached its primary efficacy endpoint, with  ASDAS disease activity scores significantly reduced at week 12 of treatment with filgotinib in patients with moderate to severely active ankylosing spondylitis.

“People with ankylosing spondylitis face serious pain and disability, and, too often, their disease does not respond adequately to existing therapies,” John McHutchison, MD, chief scientific officer and head of research and development of Gilead, said in a press release.

“These data are encouraging, suggesting filgotinib has the potential to play an important role in addressing this medical need,” he said.

Filgotinib is a highly selective inhibitor of Janus kinase 1, a signaling molecule important for the transmission of signals from immune messengers, called cytokines, and growth factors into cells. Cytokines are small proteins of importance to cell communication or signaling.

By inhibiting JAK1, filgotinib blocks the pathway leading to spinal inflammation. The compound is being co-developed by Galapagos and Gilead.

The Phase 2 randomized, placebo-controlled TORTUGA trial (NCT03117270), was a proof-of-concept trial to assess the safety and effectiveness of oral filgotinib in adults with moderate to severe ankylosing spondylitis compared to a placebo. The trial was conducted in Belgium, Bulgaria, the Czech Republic, Estonia, Poland, Spain, and Ukraine.

A total of 116 patients were enrolled and randomized to receive either filgotinib tablets of 200 mg or a placebo once daily for 12 weeks.

The study’s primary efficacy goal was to measure patients’ ankylosing spondylitis disease activity score (ASDAS), an index used to assess disease activity and that incorporates five variables: patient-reported pain, swelling, morning stiffness, global assessment, and levels of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP, blood markers of inflammation).

ASDAS disease activity scores were significantly reduced at week 12 of treatment with filgotinib, with a mean decrease in disease activity values of 1.5 vs. 0.6 for those treated with placebo. Also, more patients treated with the experimental therapy reached a 20% or higher improvement (ASAS20) compared to those treated with a placebo (76% vs. 40%, respectively).

In terms of safety, adverse events were generally mild or moderate and equally frequent in the treatment and placebo groups. No unexpected safety signals were observed, and there were no deaths, malignancies, liver events, opportunistic infections, or cases of Herpes zoster (shingles).

Detailed results from the trial will be submitted for presentation at a future scientific conference, the companies announced.

“We are excited to see that filgotinib showed strong activity across a wide range of parameters relevant for ankylosing spondylitis and was well tolerated in TORTUGA, which reinforces previous findings about the activity and tolerability profile of filgotinib in multiple inflammatory conditions,” said Walid Abi-Saab, MD, the chief medical officer at Galapagos.

Currently, the partnership between Gilead and Galapagos is advancing the clinical development of filgotinib for multiple autoimmune and inflammatory diseases.

In 2016, the investigational therapy was in several Phase 3 programs for rheumatoid arthritis, Crohn’s disease, and ulcerative colitis, as well as Phase 2 trials (in 2017) for small bowel and fistulizing Crohn’s disease, Sjögren’s syndrome, ankylosing spondylitis, psoriatic arthritis, cutaneous lupus erythematosus, lupus membranous nephropathy, and uveitis.