MADRID – (cDMARD) in a phase 3 study.
Dr. Bernard Combe
The primary outcome results of the FINCH 1 study, which were presented at the European Congress of Rheumatology, showed that significantly more patients treated with filgotinib than placebo were able to achieve 20% improvement in American College of Rheumatology response criteria (ACR20).
At week 12, an ACR20 response was achieved by 69.8% of 480 patients treated with filgotinib 100 mg/day, 76.6% of 475 treated with filgotinib 200 mg/day, and 49.9% of 475 given a matching daily placebo (P less than .0001 for both comparisons). Adalimumab (Humira; 40 mg every 2 weeks) was used as an active comparator in the trial, and 70.8% of 325 patients treated with this biologic drug achieved an ACR20.
Similar patterns were seen for the ACR50 and ACR70 responses: more than 50% of patients treated with filgotinib or adalimumab achieved an ACR50 versus 33.3% of patients treated with placebo. The ACR70 response rate was more than 30% in patients treated with either biologic, compared against 14.9% with placebo.
The percentages of patients in the filgotinib 100-mg, filgotinib 200-mg, adalimumab, and placebo arms who achieved a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or less at 12 weeks were 38.8%, 49.9%, 43.4%, and 23.4%. At 24 weeks, the rates were 53.1%, 60.6%, 50.5%, and 33.7%.
At 12 weeks, analysis showed that filgotinib 200 mg was noninferior to adalimumab in achieving a DAS28-CRP of 3.2 or less.
These study data, together with the results of two other phase 3 studies – FINCH 2 and FINCH 3 – will be used to submit a new drug application to the Food and Drug Administration for the use of filgotinib in the treatment of RA later this year, the drug’s developer, Gilead Sciences, announced on July 1. Each of the trials has addressed a different population of RA patients; while FINCH 1 looked at inadequate responders to methotrexate, FINCH 2 looked at those with an inadequate response to biologic DMARDs, and FINCH 3 recruited RA patients who were naive to methotrexate therapy.
FINCH 1 was a 1-year study, said presenting study investigator Bernard Combe, MD, PhD, professor of rheumatology at Montpellier (France) University and head of the bone and joint diseases department at the university. A total of 1,759 patients were randomized and 1,755 received study treatment with filgotinib, adalimumab, or placebo in addition to methotrexate. Data for the first 24 weeks were presented.
Dr. Combe and coauthors used hierarchical statistical testing to first compare the 200-mg dose versus placebo for the primary endpoint, and then, if positive, the percentage of patients at 12 weeks achieving a DAS28-CRP score of 3.2 or less and the score at 12 weeks on the Health Assessment Questionnaire – Disability Index (HAQ-DI), and then the DAS28-CRP again at 24 weeks. This was repeated with the 100-mg dose until finally noninferiority of the 200-mg dose versus adalimumab in DAS28-CRP at 12 weeks was tested.
Other findings included a significant reduction in radiographic progression at week 24 with both doses of filgotinib versus placebo; improvements in HAQ-DI and Functional Assessment of Chronic Illness Therapy-Fatigue scores also were seen at 12 and 24 weeks.
“The selective JAK1 inhibitor filgotinib, at doses of 200 and 100 mg per day, led to significant improvement in symptoms of RA patients with inadequate response to methotrexate,” Dr. Combe concluded. It “prevented radiographic progression, and improved physical function compared to placebo.”
Importantly, the drug was “well tolerated” and “a low frequency of venous thrombotic events, serious infections, and other adverse events of interest was observed.”
Commenting on the study during the Q&A session that followed Dr. Combe’s presentation, Roy M. Fleischmann, MD, clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas, noted that the choice of DAS28-CRP was “very unusual” as an endpoint after the ACR20 as it’s “almost always an ACR50 or 70.” There was also a “very high placebo response.”
Dr. Combe responded that he “wasn’t so surprised by the high placebo response. You know that this has been shown previously in some other trials.” As to why, he noted that there was an ongoing analysis but also proposed two reasons: First, the geographic region – with more than 1,700 patients from all over the world included in the trial, there could be variation in the placebo responses. Second, methotrexate might still be having a minor effect when the trial started.
The study was sponsored by Gilead Sciences in collaboration with Galapagos NV. Dr. Combe has received honoraria from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Sun Pharma Advanced Research, Boehringer Ingelheim, and Flexion. Dr. Combe is a shareholder in Novartis.
SOURCE: Combe B et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-8. Abstract LB0001, doi: 10.1136/annrheumdis-2019-eular.8676