Alfasigma announced positive topline results from the OLINGUITO Phase 3 clinical trial evaluating filgotinib (marketed as Jyseleca®) for the treatment of adult patients with active axial spondyloarthritis (axSpA). The oral, once-daily JAK1 preferential inhibitor met the primary endpoint and demonstrated efficacy across the full spectrum of axSpA, including both radiographic and non-radiographic forms.
The company plans to submit data from the trial to the European Medicines Agency (EMA) and UK's Medicines Healthcare products Regulatory Agency (MHRA) to seek market authorization for filgotinib in treating adults with active axSpA.
Trial Design and Results
The OLINGUITO Phase 3 trial consisted of two randomized, double-blind, multi-center, parallel-group studies of patients with active axSpA who had inadequate response to conventional or biological treatments. Study A included 258 patients with radiographic axSpA (r-axSpA), while Study B included 237 patients with non-radiographic axSpA (nr-axSpA).
Patients were randomized 1:1 to receive oral filgotinib 200 mg or matching placebo once daily for 16 weeks. The primary endpoint for both studies was the proportion of patients achieving an Assessment of SpondyloArthritis International Society 40% improvement (ASAS40) at Week 16.
"These positive OLINGUITO topline results demonstrate filgotinib's potential to address this critical unmet need for patients with axial spondyloarthritis, with only half responding adequately to current therapies," said Daniele D'Ambrosio, Chief Development Officer at Alfasigma.
Safety Profile
The safety profile was consistent with previous filgotinib studies, with no unexpected events observed. Filgotinib is currently approved for the treatment of moderate to severe active rheumatoid arthritis and ulcerative colitis in multiple territories including the European Union, United Kingdom, Japan, Taiwan, South Korea and Singapore.
Addressing Unmet Medical Need
Axial spondyloarthritis is a chronic inflammatory disease primarily affecting young adults, typically emerging during the third decade of life. The condition primarily affects the axial skeleton (spine and sacroiliac joints), causing significant pain, stiffness and reduced mobility.
Despite several efficacious anti-inflammatory treatment options, only about 40% to 50% of patients with axSpA achieve a relevant treatment response, and an even smaller proportion (approximately 10%-20%) reach remission or an inactive disease activity state within 16 to 24 weeks of treatment initiation.
Professor Xenofon Baraliakos, Head of Rheumatology at the Rheumazentrum Ruhrgebiet, Herne, Germany, commented: "These results from the OLINGUITO Phase 3 clinical trial clearly support the potential of filgotinib as a treatment option for patients living with axSpA at all stages of the disease. The burden of disease for these patients remains high as treatment options are limited."
Extended Study Design
Following the initial 16-week period, patients without risk factors entered an open-label treatment period receiving filgotinib 200 mg once daily up to Week 52. Patients achieving sustained low disease activity or inactive disease were re-randomized at Week 52 to receive double-blind filgotinib 100 mg or 200 mg up to Week 104.
For patients above 65 years of age and those with increased risk factors for cardiovascular disease or malignancies, the dose was reduced to 100 mg once daily for up to Week 104 if disease control was achieved after treatment with 200 mg once daily at Week 16.
The trial was preceded by the TORTUGA Phase 2 clinical trial, which demonstrated the safety and efficacy of filgotinib in adult patients with moderately to severely active ankylosing spondylitis (r-axSpA).
If approved, filgotinib would offer a new oral treatment option for patients with axSpA, expanding the treatment landscape in a therapeutic area marked by significant unmet needs.
