After findings from 2 randomized trials and an open-label extenstion study were released, fostamatinib (Tavalisse), anSYK inhibitor, was approved by the FDA as a second-line treatment following insufficient response to a previous therapy for patients with chronic immune thrombocytopenia.
After findings from 2 randomized trials and an open-label extenstion study were released, fostamatinib (Tavalisse), an SYK inhibitor, was approved by the FDA as a second-line treatment following insufficient response to a previous therapy for patients with chronic immune thrombocytopenia (ITP).
In FIT-1, a randomized study, 18% of patients treated with fostamatinib experienced a platelet response compared with none in the placebo arm. In FIT-2, the second randomized study, 16% of patients in the fostamatinib group had a stable platelet response compared to only 4% treated in the placebo group. The patients from these 2 trials were then included in the open-label expansion cohort (FIT-3). This study found that 23% of the patients who had received prior placebo in FIT-1 or -2 showed a platelet response to fostamatinib.
"Chronic ITP is challenging to treat because the heterogeneity of the disease makes it difficult to predict how an individual patient will respond to available treatments, and not all patients can find a treatment that works well for them. The FDA approval of fostamatinib arms physicians with a new treatment option, which works via a novel mechanism," said James Bussel, MD, lead investigator of the FIT trial program and professor emeritus of pediatrics at Weill Cornell Medicine.
There were 150 patients enrolled across both of the double-blind, phase III FIT trials. All patients received prior ITP treatment, consisting of corticosteroids (94%), immunoglobulins (53%), thrombopoietin receptor agonists (TPO-RA; 48%), or splenectomy (35%). Close to half of patients were on stable concurrent ITP therapy (47%).
FIT-3 included the patients that had no response at 12 weeks, as well as those who completed the full 24 weeks of the double-blind study. Overall, 123 patients were enrolled in the expansion cohort. Forty-four received prior placebo and 79 came from a fostamatinib-receiving arm.
Median age across the double-blind studies was 54 years (range, 20-88), and the median time since ITP diagnosis was 8.45 years. Baseline platelet counts were 16 x 109per liter. Also, 45% of patients had platelet counts below 15 x 109per liter.
Fostamatinib was started at 100 mg twice daily across all studies, with a dose escalation to 150 mg twice daily, based on the platelet counts and tolerability. Overall, 88% of patients received a dose-escalation at week 4 or later. Researchers used a primary endpoint of stable platelet response, and defined this as at least 50 x 109platelets per liter of blood on at least 4 of 6 visits between weeks 14 and 24 of the study.
In the patients receiving a prior TPO-RA, 17% showed a stable response to fostamatinib, despite the TPO-RA losing its effect for patients prior to enrollment. Rescue medication was required for 30% of those in the fostamatinib and 45% in the placebo group. Eighteen of the patients responding to fostamatinib continued to have stable platelet counts for at least 12 months.
Fewer cases of bleeding were noted with patients in the fostamatinib arm with the increase in platelet counts compared with placebo (29% vs 37%, respectively). Moderate bleeding events were experienced by Also, 9% of patients in the fostamatinib arm and by 10% for placebo experienced moderate bleeding events. Severe bleeding events were experienced in 1% and 6% of patients while serious bleeding events happened in 4% and 10% of the patients in the fostamatinib and placebo groups, respectively.
The most common all-grade adverse events (AEs) were diarrhea (31% vs 15%), hypertension (28% vs 13%), nausea (19% vs 8%), dizziness (11% vs 8%), ALT increase (11% vs 0%), respiratory infection (11% vs 6%), AST increase (9% vs 0%), and rash (9% vs 2%), in the patients with fostamatinib versus placebo, respectively
"We are excited to bring this new medicine to the population of adult patients with chronic ITP in need of additional therapies," said Raul Rodriguez, president and CEO of Rigel Pharmaceuticals, the company developing fostamatinib. "This regulatory milestone, our first product approval, validates the therapeutic effect of SYK inhibition in an autoimmune disease."