Data from two double-blind studies of the SYK inhibitor fostamatinib in adult patients with chronic/persistent immune thrombocytopenia (ITP) showed disparate results. Combined data, however, suggested that fostamatinib was associated with a better platelet response than placebo.
The studies (FIT 1 and FIT 2) were identical in design, evaluating fostamatinib in patients in whom at least one prior therapy has failed them and who had platelet counts consistently <30,000/μL. The primary efficacy endpoint in both studies was stable platelet response (defined as achieving platelet counts >50,000/μL for at least four of the six scheduled clinic visits between weeks 14 and 24 of treatment). Patients were randomized 2:1 to receive fostamatinib or placebo orally twice daily for up to 24 weeks.
In FIT 1, 51 patients received fostamatinib, and 25 patients received placebo; the rate of stable platelet response was significantly higher in the fostamatinib group (18%; n=9) than in the placebo group (0%; p=0.026).
In FIT 2, 50 patients received fostamatinib, and 24 patients received placebo; the difference in stable platelet response between the treatment cohorts was not significant: 18 percent in the fostamatinib group (n=9) and 4 percent in the placebo group (n=1; p=0.152).
However, when combining data from FIT 1 and FIT 2, the response rate was significantly higher in the fostamatinib cohort (18%; n=18/101), compared with the placebo cohort (2%; n=1/49; p=0.007). In the combined dataset, patients who experienced a stable platelet response (the primary endpoint) saw platelet counts increase from a median of 18,500/μL at baseline to >100,000/μL at week 24.
In FIT 1, AEs were reported in 96 percent of patients in the fostamatinib arm and 76 percent of patients in the placebo arm, which included gastrointestinal (GI) issues, including nausea, diarrhea, vomiting, abdominal pain (61% and 20%); nausea (29% and 4%); diarrhea (45% and 16%); infection (33% and 20%); hypertension during visit (35% and 8%); and transaminase elevation (22% and 0%).
In FIT 2, AEs occurred in 71 percent of patients in the fostamatinib group and 78 percent of patients in the placebo group, including GI issues (22% in both groups), nausea (8% and 13%), diarrhea (18% and 13%), infection (22% in both arms), hypertension during visit (20% and 17%), and transaminase elevation (6% and 0%).
Source: Rigel Pharmaceuticals press release, October 21, 2016.