SAN DIEGO, CA—Both fostamatinib regimens in the Oskira-1 Study achieved statistical improvements in ACR 20 response rate vs. placebo in patients treated with methotrexate, reported Michael Weinblatt, MD, from Brigham and Women’s Hospital, Boston, MA, at the 2013 ACR/ARHP Annual Meeting.
Fostamatinib is an oral spleen tyrosine kinase (SYK) inhibitor in development for rheumatoid arthritis (RA).
Oskira-1 was a Phase 3, 52-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study that compared fostamatinib vs. placebo +methotrexate in patients with active RA despite methotrexate therapy.
Patients were randomized to fostamatinib 100mg twice daily for 52 weeks (Group A [n=310]), or fostamatinib 100mg twice daily for 4 weeks then 150mg daily (Group B [n=304]), or placebo for 24 weeks then fostamatinib 100mg twice daily (Group C [n=304]). Non-responders at Week 12 could leave the study and enter an active extension study.
The co-primary endpoints of the study were the proportion of patients achieving ACR20 response at Week 24 and the change from baseline to Week 24 in the modified total Sharp score (mTSS). Secondary endpoints examined efficacy, safety, and tolerability up to 52 weeks.
Study analyses revealed that Groups A and B had significantly more patients achieving ACR20 at Week 24 (Group A: 152 [49.0%]; Group B: 135 [44.4%]; P<0.001) as compared to placebo (104 [34.2%]; P=0.006), with 18.2% of fostamatinib patients achieving ACR20 as early as Week 1 (vs. 4.9% placebo).
Groups A and B did not show a significant difference, however, in ∆mTSS at Week 24 (Group A: 0.45 [n=285]; Group B: 1.29 [n=277]; P=0.25) as compared to placebo (0.13 [n=278]; P= 0.17). The percentages of patients who did not progress (∆mTSS ≤ 0.5) in Groups A, B, and C were 80.7%, 77.6% and 79.5%, respectively.
“Overall response level of fostamatinib was not as large as that observed in the Phase 2 TASKi program,” remarked Dr. Weinblatt, “but safety and tolerability findings were consistent with the profile observed in earlier studies.”