Fostamatinib produces responses in ITP
Fostamatinib has produced “clinically meaningful” responses in adults with persistent or chronic immune thrombocytopenia (ITP), according to researchers.
In a pair of phase 3 trials, 18% of patients who received fostamatinib had a stable response, which was defined as having a platelet count of at least 50,000/µL for at least 4 of 6 clinic visits.
In comparison, 2% of patients who received placebo achieved a stable response.
The most common adverse events (AEs) in these trials were diarrhea, hypertension, and nausea. Most AEs were deemed mild or moderate.
These results were published in the American Journal of Hematology. The trials—known as FIT1 and FIT2—were sponsored by Rigel Pharmaceuticals, Inc., the company marketing fostamatinib.
Fostamatinib is an oral Syk inhibitor that was recently approved by the US Food and Drug Administration.
Patients and treatment
Researchers evaluated fostamatinib in the parallel FIT1 and FIT2 trials, which included 150 patients with persistent or chronic ITP who had an insufficient response to previous treatment.
In each study, patients were randomized 2:1 to receive fostamatinib or placebo for 24 weeks. In FIT1, 76 patients were randomized—51 to fostamatinib and 25 to placebo. In FIT2, 74 patients were randomized—50 to fostamatinib and 24 to placebo.
All patients initially received fostamatinib at 100 mg twice daily. Most (88%) were escalated to 150 mg twice daily at week 4 or later. Patients could also receive stable concurrent ITP therapy—glucocorticoids (< 20 mg prednisone equivalent per day), azathioprine, or danazol—and rescue therapy if needed.
The median age was 54 (range, 20-88) in the fostamatinib recipients and 53 (range, 20-78) in the placebo recipients. Sixty-one percent and 60%, respectively, were female. And 93% and 92%, respectively, were white.
The median duration of ITP was 8.7 years for fostamatinib recipients and 7.8 years for placebo recipients. Both fostamatinib and placebo recipients had a median of 3 prior unique treatments for ITP (range, 1-13 and 1-10, respectively).
Prior ITP treatments (in the fostamatinib and placebo arms, respectively) included corticosteroids (93% vs 96%), immunoglobulins (51% vs 55%), thrombopoietin receptor agonists (47% vs 51%), immunosuppressants (44% vs 45%), splenectomy (34% vs 39%), and rituximab (34% vs 29%), among other treatments.
Overall, the patients’ median platelet count at baseline was 16,000/µL. Mean baseline platelet counts were 16,052/µL (range, 1000-51,000) in fostamatinib recipients and 19,818/µL (range, 1000-156,000) in placebo recipients.
Response
The efficacy of fostamatinib was based on stable platelet response, defined as a platelet count of at least 50,000/µL on at least 4 of 6 biweekly clinic visits between weeks 14 and 24, without the use of rescue therapy.
Overall, 18% (18/101) of patients on fostamatinib and 2% (1/49) of those on placebo achieved this endpoint (P=0.0003).
In FIT1, 18% of patients in the fostamatinib arm and 0% of those in the placebo arm achieved a stable platelet response (P=0.026). In FIT2, rates of stable response were 18% and 4%, respectively (P=0.152).
A secondary endpoint was overall response, which was defined retrospectively as at least 1 platelet count ≥ 50,000/μL within the first 12 weeks on treatment.
Forty-three percent (43/101) of fostamatinib recipients achieved an overall response, as did 14% (7/49) of patients on placebo (P=0.0006).
In FIT1, the rate of overall response was 37% in the fostamatinib arm and 8% in the placebo arm (P=0.007). In FIT2, overall response rates were 48% and 21%, respectively (P=0.025).
The researchers said they observed responses to fostamatinib across all patient subgroups, regardless of age, sex, prior therapy, baseline platelet count, or duration of ITP at study entry.
