The FDA approved fostamatinib disodium hexahydrate (Tavalisse), an SYK inhibitor, as a second-line treatment for patients with chronic immune thrombocytopenia following insufficient response to a previous therapy.
The FDA approved fostamatinib (Tavalisse), an SYK inhibitor, for the second-line treatment of patients with chronic immune thrombocytopenia (ITP) following insufficient response to a previous therapy.
The agency based its approval on findings from 2 randomized trials and 1 open-label extension study, according to an announcement from Rigel Pharmaceuticals, Inc., the drug's manufacturer.
In the first randomized study, known as FIT-1, 18% of patients treated with fostamatinib experienced a platelet response compared with none in the placebo arm. In the second study, known as FIT-2, a stable platelet response was seen in 16% of patients in the fostamatinib group compared with 4% treated with placebo. Patients from these trials were could also be included in an open-label expansion cohort (FIT-3). In this study, 23% of those who received prior placebo in FIT-1 or -2 had 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," lead investigator of the FIT clinical trial program James Bussel, MD, professor emeritus of pediatrics at Weill Cornell Medicine, said in a statement. "The FDA approval of fostamatinib arms physicians with a new treatment option, which works via a novel mechanism."
One hundred fifty patients were enrolled across both double-blind, phase III FIT trials. All patients had received prior ITP treatment, which consisted of corticosteroids (94%), immunoglobulins (53%), thrombopoietin receptor agonists (TPO-RA; 48%), or splenectomy (35%). Nearly half of patients were on stable concurrent ITP therapy (47%). The FIT-3 study included those without a response at 12 weeks and those who completed the full 24 weeks of the double-blind study. Overall, 123 patients enrolled in FIT-3. Of these patients, 44 had received prior placebo and 79 were in a fostamatinib-receiving arm.
The median age of patients enrolled across the double-blind studies was 54 years (range, 20-88). The median time since ITP diagnosis was 8.45 years and baseline platelet counts were 16 x 109 per liter. Overall, 45% of patients had platelet counts below 15 x 109 per liter.
Across studies, fostamatinib was started at 100 mg twice daily, with a dose escalation to 150 mg twice daily, based on platelet counts and tolerability. Most patients (88%) were dose-escalated at week 4 or later. The primary endpoint was stable platelet response, which was defined as at least 50 x 109 platelets per liter of blood on at least 4 of 6 visits between weeks 14 and 24 of the study.
Among patients receiving a prior TPO-RA, 17% had a stable response to fostamatinib, despite the TPO-RA having lost its effect for these patients prior to enrollment. Overall, rescue medication was required by 30% of those in the fostamatinib and for 45% of patients in the placebo group. Of those responding to fostamatinib, 18 continued to have stable platelet counts for 12 months or longer.
With the increase in platelet counts, there were fewer cases of bleeding experienced by patients in the fostamatinib arm compared with placebo (29% vs 37%, respectively). Moderate bleeding events were experienced by 9% of patients in the fostamatinib arm and by 10% for placebo. Severe bleeding events were seen in 1% and 6% of patients and serious bleeding events occurred in 4% and 10% of patients in the fostamatinib and placebo groups, respectively.
The most frequently observed all-grade adverse events (AEs) with fostamatinib versus placebo, respectively, 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%).
"We are excited to bring this new medicine to the population of adult patients with chronic ITP in need of additional therapies," Raul Rodriguez, president and CEO of Rigel Pharmaceuticals, said in a statement. "This regulatory milestone, our first product approval, validates the therapeutic effect of SYK inhibition in an autoimmune disease."
Rigel Pharmaceuticals plans to have fostamatinib ready for commercial launch in late May 2018.