Stanford Health Care and Keito University School of Medicine conduct clinical trial assessing the use of filgotinib in a large 24-week study to treat rheumatoid arthritis patients. Their study results were published in the July 23 edition of JAMA.
As reported in MedicalXpress, the study’s author, Mark Genovese, MD, professor of immunology and rheumatology at Stanford, was also the study’s principal investigator.
Patients struggling with rheumatoid arthritis are reported to benefit 70% of the time, according to clinical trials results, when taking small-molecule drugs in pill form, such as methotrexate. However, the real-world adherence to any of these drugs approaches 50%.When small-molecule drugs fail, patients often are switched to expensive biologic drugs, such as Humira. However, these drugs frequently may not work or the patient may be subject to severe side effects.
Hence this study was designed for the rheumatoid arthritis patient that didn’t get any relief from conventional small-molecule drugs or from injectable biologic drugs—could filgotinib provide relief?
This clinical trial was conducted in 114 centers in 15 countries primarily in North America and Europe, reported MedicalXpress.
At an average age of 56, the 449 study patients were overwhelmingly female (80%). The patients were randomized to 1 of 3 study arms with the following doses: 200 milligrams of filgotinib, 100 milligrams of filgotinib or a placebo for 24 weeks. Each patient was afflicted with moderately to severely active rheumatoid arthritis.
The sponsors sought to observe improvements at 12 weeks into the study based on a 20% of a measure called ACR20—an indication of joint swelling and tenderness established by the American College of Rheumatology. The secondary outcome score was based on a test called the DAS28-CRP.
Those receiving filgotinib fared better than those in the placebo group. For example, the low and high-dose filgotinib groups achieved the primary endpoint: 20% improvement in symptoms as measured by the ACR20. 66% of participants on 200 milligrams of filgotinib, and 57.5% of those on 100 milligrams, fulfilled this criterion versus only 31.1.% of these on the placebo.
Notable improvements were exhibited on the DAS28-CRP at both 12 and 24 weeks (secondary outcomes). Principal investigator Mark Genovese reported that by 12 weeks, 40.8% of those on the 200 milligram dose of filgotinib and 37.3% of those on 100 milligrams had reached the desired status of low disease activity per the DAS28-CRP measurement. The placebo group only achieved 15.5%.
Interestingly by week 12 of the study reported MedicalXpress, the high-dose and low-dose filgotinib recipients were scoring 22.4% and 25.5% respectively for outright remission; placebo was only at 8.1% for the DAS28-CRP scoring. By week 24, high-dose recipients had a remission rate of 30.6%; low-dose recipients 26.1% and placebo 12.2%
What is Filgotinib?
It is a selective JAK-1 inhibitor. It functions by preferentially blocking 1 of a set of 4 closely related enzymes needed for select inflammatory signaling processes within cells. Also known as GLPG0634, it is a drug currently under investigation for the treatment of rheumatoid arthritis (RA) and Crohn’s disease. It was developed by Belgian-Dutch biotech company Galapagos NV. TrialSite News wrote about Galapagos recently in regards to their $5 billion licensing deal with Gilead.
A Janus Kinase inhibitor with selectivity for subtype JAK1 of this enzyme. Less selective JAK inhibitors (e.g. tofacitinib) are already being marketed. They reveal long-term efficacy in the treatment of various inflammatory diseases. However, the lack of selectivity can lead to dose-limiting side effects. It is thought that potential inhibition of all JAK isoenzymes is beneficial in rheumatoid arthritis. However, pan-JAK inhibition might also lead to unwanted side effects that might not outweigh its benefits. Hence, the driver for investment in the development of newer and more selective inhibitors, such as filgotinib.
Mark Genovese reports that “this novel drug works exceptionally well in patients who’ve already failed traditional therapies for rheumatoid arthritis.
Mark Genovese, Principal Investigator