Consistent Efficacy Demonstrated By Avatrombopag in Immune Thrombocytopenia (ITP) Regardless of the Number of Lines of Prior ITP Treatment

Background: Clinical management of ITP depends on both disease severity and risk of bleeding. Treatment typically is considered when platelet counts (PC) fall below 30,000/µL, with a target PC of ≥50,000/µL to mitigate the risk of bleeding. The standard-of-care after failure of 1st line therapy (corticosteroids or intravenous immunoglobulin) has been shifting from splenectomy and rituximab, toward an increased use of thrombopoietin receptor agonists (TPO-RAs), as supported by the recent American Society of Hematology guidelines (Neunert 2019). The TPO-RAs eltrombopag (ELT) and romiplostim (ROMI) have well understood efficacy profiles, but ELT has an FDA boxed safety warning for hepatotoxicity, necessitating hepatic function monitoring. Additionally, ELT is an orally administered chelating agent that requires dosing two hours prior to, or four hours after, meals containing polyvalent cations such as calcium or magnesium to mitigate clinically relevant effects on the pharmacokinetic profile (ELT prescribing information). In addition, ROMI, an injection, is typically is administered by a health care practitioner. Avatrombopag (AVA) is an oral TPO-RA for patients with ITP. In clinical trials, AVA rapidly increased platelet counts as early as day 5 and maintained the median PC in the target range (50 to 150×109/L) with chronic dosing. Further, it has an exposure-adjusted safety profile generally comparable to placebo and no boxed safety warning for hepatotoxicity. AVA does not chelate polyvalent cations; therefore it is administered with food, and there are no restrictions regarding meal composition. Aims: To understand how the number of prior ITP treatments impacted the efficacy of avatrombopag in a Phase 3 study. Methods: A 6-month, multicenter, randomized, double-blind, Phase 3 study enrolled 32 AVA and 17 placebo-treated (PBO) patients with ITP. The primary endpoint was the median number of cumulative weeks of platelet count (PC) response (achieving a PC ≥50,000/µL) over the course of the study without rescue medication. Patients receiving any rescue medication during the study were deemed to be non-responders for the remainder of the study. Due to the limited number of study participants, for the post-hoc analyses reported here, the study population was segmented by whether a patient had received Results: Table 1 shows key differences in baseline characteristics between each group, suggesting that those receiving ≥3 prior ITP medications may have had more refractory disease. The median cumulative number of weeks of PC response for the entire population during the study was 12.4 vs. 0.0 for AVA and PBO respectively (p Conclusions: In this Phase 3 study, the number of prior ITP treatments a patient had received did not seem to definitively predict PC response to AVA, though on some measures the group receiving Download : Download high-res image (520KB) Download : Download full-size image Disclosures Vredenburg: Dova Pharmaceuticals: Current Employment. Tian: Dova Pharmaceuticals: Current Employment. Jamieson: Dova Pharmaceuticals: Current Employment. McCrae: Rigel: Consultancy; Dova: Consultancy; Momenta Pharmaceuticals: Consultancy; Novartis: Honoraria.