Positive results from the Fostamatinib in Thrombocytopenia (FIT) Phase 3 clinical program of fostamatinib disodium hexahydrate (Tavalisse) were published in the American Journal of Hematology
On April 17, the U.S. Food and Drug Administration (FDA) approved fostamatinib disodium hexahydrate
for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
The article, “Fostamatinib for the treatment of Adult Persistent and Chronic Immune Thrombocytopenia: Results of Two Phase 3, Randomized, Placebo-Controlled Trials
,” includes the work of principal investigator James Bussel, MD, professor emeritus of pediatrics at Weill Cornell Medicine and a consultant and paid member of the advisory board for Rigel Pharmaceuticals, Inc.1
In the 2 parallel, multicenter, randomized, double‐blind, placebo‐controlled trials (FIT1 and FIT2), patients with persistent/chronic ITP were randomized 2:1 to fostamatinib (n
=101) or placebo (n
=49) at 100mg twice a day (BID) for 24 weeks with a dose increase in non‐responders to 150mg BID after 4 weeks. Stable response (platelets ≥50,000/μL at ≥4 of 6 biweekly visits, weeks 14‐24, without rescue therapy) served as the primary endpoint for the program.
Stable responses occurred in 18% of patients on fostamatinib vs. 2% on placebo (P=0.0003). Overall responses occurred in 43% of patients on fostamatinib vs. 14% on placebo (P=0.0006). Median time to response was 15 days (on 100mg bid), and 83% responded within 8 weeks.
Fostamatinib produced clinically‐meaningful responses in ITP patients, including those who failed splenectomy, thrombopoietic agents, and/or rituximab.
Patients who completed the 24-week study treatment in either FIT-1 or FIT-2 were permitted to enroll in the long-term, open-label extension (OLE) study (FIT-3); non-responders who discontinued the study after 12 weeks for lack of efficacy and had received 150 mg BID of study drug for ≥4 weeks could also enroll in FIT-3.
"These data demonstrate that [Fostamatinib disodium hexahydrate] offers the potential for a rapid, robust and durable platelet response, which is why we are excited to soon make it available to the population of patients in need of alternate treatment options," said Anne-Marie Duliege, M.D., Chief Medical Officer of Rigel Pharmaceuticals, Inc. in a press release
. "[Fostamatinib disodium hexahydrate] is the first approved treatment option that targets the SYK pathway, which is the main pathway involved in platelet destruction in ITP."
This pair of Phase 3 studies included the first 2 trials to evaluate second- or third-line treatment for ITP in the current era of widespread use of TPO-RA and rituximab. In an exclusive interview with Rare Disease Report
, Dr. Bussel explained what the approval of fostamatinib means for the ITP community: “It’s definitely a promising therapy. I believe that it will be very good to have another treatment with a unique mechanism of action that can be taken orally without a specific diet. This is very important for the field. We will see how it impacts the disease space going forward.”
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- Fostamatinib for the Treatment of Adult Persistent and Chronic Immune Thrombocytopenia: Results of Two Phase 3 Randomized, Placebo-Controlled Trials. https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.25125 Accessed April 30, 2018.