WASHINGTON — According to researchers at the American College of Rheumatology Annual Meeting, filgotinib, used as monotherapy or in combination with methotrexate, improved patient-reported outcomes for those with active rheumatoid arthritis. In addition, the drug has shown potential for other uses in rheumatoid arthritis, as well as other diseases.
Filgotinib effective in DARWIN studies
“This selected [Janus kinase 1] JAK1 inhibitor was effective in reducing the signs and symptoms of disease, but also resulted in substantial improvement in function, disability, fatigue and other aspects that are important to patients and the management of their disease,” Mark C. Genovese, MD, in the Division of Immunology and Rheumatology at Stanford University Medical Center, told Healio Rheumatology.
Mark C. Genovese
As part of the double-blind DARWIN studies, Genovese and colleagues randomized patients with active rheumatoid arthritis (RA) — who had inadequate response to methotrexate — to receive placebo or either 50 mg, 100 mg or 200 mg of filgotinib for a duration of 24 weeks. Patients received filgotinib as an add-on to methotrexate therapy for DARWIN 1 (n = 594) and received filgotinib as monotherapy for DARWIN 2 (n = 283). In DARWIN 1, the researchers assessed both once and twice daily regimens. At baseline, the mean health assessment questionnaire disability index (HAQ-DI) was 1.74 for DARWIN 1 and 1.81 for DARWIN 2. At week 12, the researchers reassigned patients to a 100-mg daily dose for those on placebo in DARWIN 1 or on 50-mg daily dose in DARWIN 1 or 2 whose tender and swollen joint counts did not improve by at least 20%. In DARWIN 2, all patients on placebo were reassigned to a 100-mg daily dose. The researchers evaluated patient-reported outcomes (PROs) — including disease activity and pain, physical function, fatigue and SF-36.
For both studies, the researchers found filgotinib was associated with an improvement in PROs. After 1 week, the 200-mg daily dose was associated with improvement for HAQ-DI and patient VAS scores for global disease and pain. After 4 weeks, the 200-mg dose was associated with improvement in functional assessment of chronic illness therapy (FACIT)-fatigue and the SF-36 physical component summary (PCS) score. For both studies, the 100-mg daily dose was associated with improvement for patient global assessment after 1 week and improvement for FACIT after 4 weeks. For DARWIN 2, the SF-36 PCS score improved after 4 weeks. After 12 weeks, these responses were maintained through week 24. At week 24, the effect was comparable between 100-mg and 200-mg therapy as well as between add-on and monotherapy.
Filgotinib shows potential for other uses
After entering a partnership last year with Galápagos NV, Gilead has continued to develop filgotinib, an oral Janus kinase 1 (JAK1) inhibitor, for the treatment of rheumatoid arthritis (RA) and Crohn’s disease.
“One of the things that appealed to us about filgotinib was that we saw this as a kind of foundation, or building block on which we could begin to build other regimens, or combination regimens that might increase the percentage of patients who have a high-level response in RA,” John Sargent Sundy, MD, PhD, vice president of Clinical Research Inflammation & Respiratory Therapeutics at Gilead Sciences Inc., told Healio Rheumatology.
John Sargent Sundy
Separately Sundy said the company also has been studying animal models of RA through a collaboration with Gary S. Firestein, MD, and his group at University of California, San Diego’s School of Medicine, and discovered that oxidative stress is a key component of the inflammatory response, kicking off a series of gene expression activity that eventually leads to inflammation, fibrosis and changes in cell metabolism. In addition to exploring filgotinib and other drugs in its pipeline for RA, Gilead is also interested in investigating treatment for other diseases like lupus, psoriasis and psoriatic arthritis.
“How do we put together a program for patients, recognizing that some will have well-controlled disease with a single drug and others may need more aggressive therapy?” Sundy said. “I think what is interesting about this is having some small molecules that you could potentially combine together, begins to make combination therapies more feasible in ways that might be harder to do with multiple different biologics.” – by Kristine Houck, ELS, and Will Offit
Genovese MC, et al. Abstract #3025. Presented at: American College of Rheumatology Annual Meeting; Nov. 11-16, 2016; Washington.
Disclosures: Genovese reports he is a consultant for both Gilead and Galapagos. Sundy reports he is a Gilead employee and stockholder.