The European Medicines Agency’s Committee for Medicinal Products for Human Use has issued a positive opinion for a Marketing Authorization Application of fostamatinib disodium hexahydrate for the treatment of adult patients with chronic immune thrombocytopenia who are refractory to other treatments.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for a Marketing Authorization Application of fostamatinib disodium hexahydrate (fostamatinib; Tavalisse) for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who are refractory to other treatments.1
The recommendation is based on findings from the FIT Phase III clinical program, which included the randomized placebo-controlled FIT1 and FIT2 trials, as well as the open-label extension FIT3 trial. The application was supported by data from 163 patients with ITP, and also by a safety database of more than 4600 individuals across all other indications in which fostamatinib has been evaluated.
In FIT1, 18% of patients treated with fostamatinib experienced a platelet versus none in the placebo arm.2 In FIT2, a stable platelet response was seen in 16% of patients on fostamatinib group compared with 4% of patients who were treated with placebo. In FIT3, results showed that 23% of those who received prior placebo in FIT1 or FIT2 had a platelet response to fostamatinib.3
The European Commission will now review the recommendation and will issue a decision on the approval within an estimated 70 days. The FDA approved fostamatinib as a second-line treatment for patients with chronic ITP following insufficient response to a previous therapy in April 2018, also based on the FIT findings.
"We are extremely encouraged by the CHMP's positive opinion and look forward to the final decision on our MAA from the European Commission," Raul Rodriguez, president and CEO of Rigel Pharmaceuticals, the developer of fostamatinib, said in a press release. "We are excited by the potential to provide adult chronic ITP patients in Europe with a new treatment option that addresses the primary cause of their disease. Our European partner, Grifols, is preparing diligently for a prospective commercial launch in 2020."
A total 150 patients were enrolled across both double-blind, phase III FIT trials. All patients had received prior ITP treatment, which consisted of corticosteroids (94.5%), immunoglobulins (53%), thrombopoietin receptor agonists (TPO-RA; 49%), or splenectomy (36.5%).
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 53.4 years.
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.
With the increase in platelet counts, there were fewer cases of moderate or severe bleeding experienced by patients in the fostamatinib arm compared with placebo (9% vs 16%, respectively).
The most frequently observed all-grade adverse events with fostamatinib versus placebo, respectively, were diarrhea (31% vs 15%), hypertension (28% vs 13%), nausea (19% vs 8%), dizziness (11% vs 8%), alanine transaminase increase (11% vs 0%), and respiratory infection (11% vs 6%).