Efficacy and Safety of Avatrombopag in Japanese Adults with Chronic Immune Thrombocytopenia: Open-Label, Phase 3 Study
Authors: Yamaguchi Hiroki , Iino Masaki , Imamura Yutaka , Kowata Shugo , Yamamoto Ryusuke , Yamanouchi Jun , Fujii Masato , Zhang Jessica , Tomiyama Yoshiaki , Jamieson Brian 
Published: December 2024

Introduction: Avatrombopag (AVA) is an orally administered thrombopoietin receptor (TPO-RA) agonist widely approved for the treatment of adults with chronic immune thrombocytopenia (ITP). This study aims to assess AVA in Japanese patients with chronic ITP.
Methods: This Phase 3, multicenter, open-label study (a 26-week core phase [completed] followed by an extension phase [ongoing until market authorization in Japan]) evaluates the efficacy and safety of AVA (initial dose 20 mg/day) in Japanese adults (aged ≥18 years) with chronic ITP (≥12 months duration), insufficient response to prior treatment (investigator assessed), and an average of two platelet counts (PCs) &lt;30×109/L. The core phase included a 1-day baseline assessment, a 6-week dosage titration phase, a 12-week concomitant medication reduction phase, and 8 weeks of maintenance treatment. The primary endpoint was the cumulative number of weeks in which the PC was ≥50×109/L during 26 weeks of treatment in the absence of rescue therapy. The key secondary endpoint was the platelet response rate at Day 8 (percentage of patients with a PC ≥50×109/L). Additional efficacy endpoints included durable platelet response (six of eight weekly PC ≥50×109/L during the last 8 weeks of treatment in the absence of rescue therapy), continuous platelet response (the number of consecutive weeks of platelet response ≥50×109/L in the absence of rescue therapy), International Working Group (IWG) complete platelet response (PC ≥100×109/L and absence of bleeding or rescue therapy at each analysis visit), IWG platelet response (PC ≥30×109/L and at least a two-fold increase in baseline platelet count and absence of bleeding or rescue therapy at each analysis visit), and concomitant ITP medication reduction/discontinuation. The primary, key secondary, and additional efficacy endpoints, and the maximum grade of treatment-emergent adverse events [TEAEs] and bleeding events in the core phase [using the World Health Organization (WHO) Bleeding Scale]) are reported.
Results: In total, 19 patients (mean age 56.0 years; 78.9% female) were enrolled at 19 sites in Japan; 15 patients (78.9%) completed the core phase, and four patients (21.1%) discontinued the study (due to: adverse events [one patient], lack of efficacy at the highest dose [one patient], and use of prohibited concomitant medication [two patients]). Eight patients (42.1%) had a baseline PC ≤15×109/L, and nine patients (47.4%) used concomitant ITP medication at baseline. Three patients (15.8%) had at least one previous significant bleeding event prior to the core phase. The mean cumulative number of weeks of platelet response was 13.47 weeks (95% confidence interval [CI]: 9.13, 17.80). At Day 8, 12 patients (63.2%; 95% CI: 38.4, 83.7) had a platelet response (PC ≥50×109/L), and eight patients (42.1%; 95% CI: 20.3, 66.5) had a durable platelet response during the last 8 weeks of the core phase. The mean maximum duration of continuous platelet response was 7.63 weeks (standard deviation: 6.907). IWG complete platelet response and IWG platelet response were achieved by 5 of 19 (26.3%) and 9 of 19 (47.4%) patients by Day 8, and by 4 of 15 (26.7%) and 9 of 15 (60.0%) patients, respectively, at Week 26. Of the nine patients who used concomitant ITP medications at baseline, five (55.6%) reduced their use, and one patient discontinued use. Most TEAEs were Grade 1 or 2 (15 patients, 79.0%). A Grade 3 TEAE occurred in two patients (diffuse large B-cell lymphoma and heavy menstrual bleeding) and a Grade 4 TEAE (autoimmune hepatitis) occurred in one patient. No deaths or thromboembolic events were reported. Most bleeding events were mild (WHO Grade 1); no patients had a WHO Grade 3 or 4 bleeding event.
Conclusion: AVA effectively provided a rapid and durable platelet response and induced complete platelet response by IWG criteria in Japanese patients with chronic ITP. Furthermore, AVA was well tolerated in these patients. These data add to the existing body of evidence supporting the efficacy and safety of AVA in different populations.