TAVALISSE Rx

Tavalisse was studied in two placebo-controlled efficacy and safety studies (referred to as FIT-1 [ClinicalTrials.gov Identifiers: NCT02076399] and FIT-2 [NCT02076412]), and in an open-label extension study referred to as FIT-3 (ClinicalTrials.gov Identifier: NCT 02077192).

Randomized, Placebo-Controlled Studies

• A total of 150 patients with persistent or chronic ITP, who had an insufficient response to previous treatment were enrolled in two identical, double-blind, placebo-controlled studies that were conducted in different countries. 
• Patients were randomized 2:1 to Tavalisse or placebo for 24 weeks; randomization was stratified with respect to prior splenectomy and severity of thrombocytopenia. 
• Stable concurrent ITP therapy was allowed, and rescue therapy was permitted, if needed. 
• All patients initially received the study drug at 100 mg twice daily (or matching placebo). 
• Based on platelet count and tolerability, dose escalation to 150 mg twice daily (or matching placebo) was undertaken in 88% of patients at Week 4 or later. 
• Patients who did not respond to treatment after 12 weeks, as well as patients who completed the 24-week double blind study, were eligible to enroll in open-label extension study (FIT-3).
• At baseline, the median platelet count was 16×10⁹/L (with almost half [45]% <15×10⁹/L) and 47% were on stable ITP therapy.
• In Study FIT-1 (n=76), 51 patients were randomized to the Tavalisse group and 25 to the placebo group.
• In Study FIT-2 (n=74), 50 patients were randomized to the Tavalisse group and 24 to the placebo group.
• The efficacy of Tavalisse was based on stable platelet response (at least 50×10⁹/L on at least 4 of the 6 visits between Weeks 14 to 24). 
• Results in FIT-1 showed 18% of the Tavalisse group achieved stable platelet response vs 0% in the placebo group (P =.03). While in FIT-2, 16% of the Tavalisse group achieved stable platelet response vs 4% in the placebo group (P-value not significant).

Extension Study

• The FIT-3 trial is an open label extension study. 
• Patients from FIT-1 and FIT-2 who completed 24 weeks of treatment, or who did not respond to treatment any time after 12 weeks, were eligible to enroll in this study.
• Patients designated as responders (defined as achievement of platelet count of at least 50×10⁹/L) at the time of roll over continued in the extension study at their current trial dose and regimen.
• Patients who entered the extension study as non-responders (defined as platelet count <50×10⁹/L) received Tavalisse 100 mg twice daily regardless of their dose and regimen in the prior study.
• For the FIT-3 trial (n=123), 44 patients were previously randomized to placebo; 79 patients were previously randomized to Tavalisse.
• Stable response was prospectively defined as no 2 visits (at least 4 weeks apart) with a platelet count <50×10⁹/L, without an intervening visit with a platelet count of at least 50×10⁹/L, within a period of 12 weeks following initial achievement of the target platelet count.
• Sixty-one of the 123 subjects (50%) have discontinued from the study early.
• In the prospective analysis, the 44 patients treated with placebo in the prior study were evaluated for stable response for Tavalisse. Ten of these subjects (23%) met the criteria for stable response.

Among the patients who achieved stable response in FIT-1, FIT-2 and FIT-3 trials, 18 patients maintained the platelet count of at least 50×10⁹/L for 12 months or longer.