Fostamatinib (Tavalisse) Photo courtesy of

The US Food and Drug Administration (FDA) has granted approval for the oral SYK inhibitor fostamatinib disodium hexahydrate (Tavalisse™).

Fostamatinib is now approved for the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Rigel Pharmaceuticals, Inc., plans to launch fostamatinib in the US in late May 2018.

The FDA’s approval of fostamatinib was supported by data from the FIT clinical program, which included 2 randomized, placebo-controlled, phase 3 trials—FIT-1 (NCT02076399) and FIT-2 (NCT02076412)—and an open-label extension study—FIT-3 (NCT02077192)—as well as an initial proof-of-concept study.

FIT-1 and FIT-2

FIT-1 and FIT-2 included 150 patients with persistent or chronic ITP who had an insufficient response to previous treatment. The patients had a median age of 54 (range, 20 to 88), 61% were female, and 93% were white.

Prior ITP treatments included corticosteroids (94%), immunoglobulins (53%), and thrombopoietin receptor agonists (48%). Thirty-five percent of patients had undergone splenectomy.

The patients’ median platelet count at baseline was 16 x 10⁹/L, and 47% were on stable ITP therapy.

In each study, patients were randomized 2:1 to receive fostamatinib or placebo for 24 weeks. In FIT-1, 76 patients were randomized—51 to fostamatinib and 25 to placebo. In FIT-2, 74 patients were randomized—50 to fostamatinib and 24 to placebo.

All patients initially received fostamatinib at 100 mg twice daily. Most (88%) were escalated to 150 mg twice daily at week 4 or later. Patients could also receive stable concurrent ITP therapy—glucocorticoids (< 20 mg prednisone equivalent per day), azathioprine, or danazol—and rescue therapy if needed.

The efficacy of fostamatinib was based on stable platelet response, defined as a platelet count of at least 50 x 10⁹/L on at least 4 of the 6 visits between weeks 14 to 24.

In FIT-1, 18% of patients in the fostamatinib arm and 0% of those in the placebo arm achieved a stable platelet response (P=0.03).

In FIT-2, 16% of patients in the fostamatinib arm and 4% in the placebo arm achieved a stable platelet response. In this trial, the between-arm difference was not statistically significant.

For both studies, the incidence of bleeding was 29% in the fostamatinib arm and 37% in the placebo arm. The rate of severe bleeding-related events was 1% and 6%, respectively, and the rate of serious bleeding-related events was 4% and 10%, respectively.

FIT-3

Patients from FIT-1 and FIT-2 could enroll in FIT-3 if they completed 24 weeks of treatment or did not respond to treatment any time after 12 weeks.

Patients who were in response at the time of roll over (those who had achieved a platelet count of at least 50 x 10⁹/L) continued in FIT-3 at their current dose and regimen.

Non-responders received fostamatinib at 100 mg twice daily regardless of their dose and regimen in the prior study.

In all, 123 patients were enrolled—44 previously randomized to placebo and 79 previously randomized to fostamatinib. Half of patients (n=61) discontinued the study early.

Of the 44 patients with prior placebo, 10 (23%) had a stable platelet response to fostamatinib. This included a patient who was a responder to placebo in the prior study.

In FIT-3, stable platelet response was defined as having no 2 visits, at least 4 weeks apart, with a platelet count less than 50 x 10⁹/L without an intervening visit with a platelet count of at least 50 x 10⁹/L (unrelated to rescue therapy) within a period of 12 weeks after the patient’s initial achievement of the target platelet count.

Of all the responders in the FIT trials, there were 18 who maintained a platelet count of at least 50 x 10⁹/L for 12 months or longer.

For more details on these trials and fostamatinib, see the full prescribing information, which is available at www.TAVALISSE.com.

Fostamatinib approved to treat adults with chronic ITP