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The US Food and Drug Administration (FDA) has accepted a new drug application (NDA) for the use of fostamatinib disodium (Tavalisse™) in the treatment of patients with chronic/persistent immune thrombocytopenia (ITP).
Fostamatinib is an oral spleen tyrosine kinase (SYK) inhibitor that investigators believe may address an underlying autoimmune cause of ITP by impeding platelet destruction.
Rigel Pharmaceuticals, the drug’s developer, anticipates an action date by the FDA of April 17, 2018.
The FDA previously granted fostamatinib orphan drug designation.
Data from 3 clinical studies support the new drug application. Study 047 and 048 were randomized placebo-controlled trials, and study 049 was an open-label extension study.
Together with an initial proof of concept study, the application included data on 163 ITP patients. Fostamatinib has been evaluated in over 4,600 individuals across all indications.
The patients enrolled in studies 047 and 048 had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL.
In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.
Study 047
In this study, 51 patients were randomized to fostamatinib and 25 to placebo.
The median platelet counts at baseline were 15,000/uL and 16,000/uL in the fostamatinib and placebo arms, respectively.
The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.
The primary efficacy endpoint in both study 047 and 048 was a stable platelet response, defined as achieving platelet counts greater than 50,000/uL for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.
In study 047, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).
Study 048
Fifty patients were randomized to fostamatinib and 24 to placebo.
Patients’ median platelet counts at baseline were 16,000/uL and 21,000/uL in the fostamatinib and placebo arms, respectively.
The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.
In this study, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).
However, when the data from study 047 and 048 were combined, the response rate was significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).
"The FDA acceptance for filing of our NDA is an exciting milestone for Rigel," Raul Rodriguez, Rigel's president and chief executive officer, said.
The approval of fostamatinib “will provide a new treatment option for patients with chronic or persistent ITP,” he affirmed. “We look forward to working closely with the FDA as they review our submission."
