Two-Year Safety and Efficacy Outcomes with Fostamatinib in Adult Patients with Immune Thrombocytopenia (ITP): Open-Label Extension to Phase 3 Trial Program

Introduction. The phase 3 randomized, placebo-controlled trials of the SYK inhibitor fostamatinib in adult patients with ITP were followed by an open-label extension (OLE) study to examine durability of response to fostamatinib and to allow patients in the placebo group in the phase 3 trials to crossover to fostamatinib. This abstract provides an additional year of data from the OLE study in patients with up to 3 years of fostamatinib treatment.

Methods. Patients were adults with persistent or chronic ITP who had failed ≥1 prior therapy and had ≥3 platelet counts below 30,000/μL at screening. Patients initiated fostamatinib treatment at 100mg BID PO and increased to 150 mg BID based on tolerability and if platelets were <50,000/μL after 1 month. A stable platelet response was defined as a platelet count ≥50,000/μL that was maintained during the second 12-week period of fostamatinib treatment. The pre-specified analysis in the OLE study was the achievement and maintenance of a stable platelet response for 12 months. A post-hoc analysis was conducted on overall response, defined as achieving ≥1 platelet count of ≥50,000/µL within 12 weeks of beginning active treatment. All analyses excluded counts within 4 weeks of a rescue therapy. The data cutoff is 8 March 2018.

Results. In the OLE study, 123 patients received fostamatinib, including 44 who had received placebo in the phase 3 studies. At baseline, the median age was 52 years (range 20-88), and 7% had persistent ITP (<12 months duration). The median duration of disease was 8.4 years, and the median platelet count was 16,000/μL at the start of treatment. Prior to the phase 3 studies, patients had tried a median of 3 (range 1-13) unique ITP treatments including splenectomy (35%; median 13 years earlier), corticosteroids (95%), immunoglobulins (53%), TPO-RA (47%), immunosuppressants (43%), and rituximab (32%).

The median duration of fostamatinib exposure was 8.9 months (range 1.5-41.3). The median treatment compliance was 98%. At the time of analysis, 42 of 123 subjects (34%) continued fostamatinib treatment. Main reasons for discontinuation included lack of a platelet response after Week 12 (36%), study-specific adverse event (AE) (7%), and other AEs (7%).

Of 27 patients with a stable response, 21 (78%) have maintained the response at Month 12 of fostamatinib treatment, and 15 (56%) at Month 24. At Month 12, median platelet count for the 49 subjects with data at that time point was 72,000/µL (range: 9000-333,000 µL). For the 32 subjects with data at Month 24, median platelet count was 80,500/µL (range: 7000-315,000/µL). See figure. An overall platelet response was achieved by 57/123 (46%) patients.

AEs were reported by 95 (77%) patients and were mild/moderate in 92 (75%). See table. The most common AEs were diarrhea and hypertension, which were manageable with targeted treatment, fostamatinib dose modifications, or treatment withdrawal (5 patients withdrew due to diarrhea and none due to hypertension). Serious adverse events (SAE) were reported in 28 patients (23%), were considered unrelated to fostamatinib in 23 patients (19%) and included bleeding-related SAEs in 11 subjects (9%), thrombocytopenia in 6 subjects (5%), epistaxis in 3 (2%), sepsis in 2 (2%) and transaminases increased in 2 (2%). Adverse events were consistent with those reported during the placebo-controlled trials.

Conclusion. In this open-label extension study of the two phase 3, placebo-controlled trials, 56% of subjects with a stable response maintained the response for ≥24 months. No new safety signals have been detected during long-term treatment of ITP with fostamatinib.

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