Interim Analysis of Platelet Response in a Prospective Phase 4 Study in Adult Immune Thrombocytopenia (ITP) Subjects after Switching from Eltrombopag (ELT) or Romiplostim (ROMI) to Avatrombopag (AVA)

Abstract

Background: Three thrombopoietin receptor agonists (TPO-RAs) [eltrombopag, romiplostim, and avatrombopag] are currently approved in the United States (US) and Europe for the treatment of ITP in adult patients. ROMI is administered via injection whereas ELT and AVA are oral medications. Polyvalent cations significantly limit the bioavailability of ELT; therefore, patients must follow rigid dietary restrictions. AVA is taken with meals and does not have food-type or timing restrictions, aligning with reported patient preferences for ITP treatments. 1 A recent retrospective study of heavily pre-treated ITP patients at 4 large US tertiary care medical centers demonstrated that 91% of AVA patients who switched from ELT and 94% who switched from ROMI achieved a platelet response (platelet count (PC) ≥50 x 10 9/L) regardless of the reason for switch. 2 This study required a < 30-day gap between ELT or ROMI discontinuation and initiation of AVA. Platelet count response to AVA following an immediate switch from another TPO-RA has not been previously reported in a prospective study. The current study aims to evaluate the safety and efficacy of immediately switching to AVA from other TPO-RAs as well as capture patient-reported outcomes of treatment satisfaction and convenience. Methods: This is an interim analysis of a prospective, multi-center, open-label Phase 4 study conducted in the US (NCT04638829). Subjects who have been receiving ELT or ROMI ≥90 days prior to study entry are enrolled and immediately switched to AVA. The main inclusion criteria: age ≥18 years; subjects have been undergoing treatment for primary ITP with ELT or ROMI for at least 90 days prior to the screening visit and have a desire to switch therapy; subjects have had a previous response to either ELT or ROMI, defined as at least 2 platelet counts ≥50×10 9/L. The primary endpoint is occurrence of adverse events and serious adverse events. Clinic Visits were mandated per protocol at Baseline (BL), Days 15 (D15), 30 (D30), 60 (D60), and 90/End of Study (D90/EOS), and PCs were obtained at each timepoint. The interim analyses reported here evaluate the PC response to AVA following the switch from either ELT or ROMI. Results: As of April 1, 2023, 51 patients were screened and 47 enrolled. 35 completed the study, 3 dropped out, and 6 are on-going. The mean age at enrollment was 58 years, the median (min,max) time since ITP diagnosis was 2.88 years (0.2,31.0), 28/47 (60%) were female, 34/47 (72%) were Caucasian, and 5/47 (11%) had a previous history of splenectomy. 62% of patients were switched to AVA from ELT (median prior treatment duration 42 weeks (range 12 - 442 weeks); median daily dose 50 mg) and 38% from ROMI (median prior treatment duration 81 weeks (range 12 - 468 weeks); median weekly dose ≤3 µg). Baseline platelet counts revealed that patients were generally well-controlled on prior TPO-RA therapies when switched with a mean platelet count of 152×10 9/L and median platelet count of 130×10 9/L in the overall study population. Safety results will be reported when the study is complete. PC values for the Entire Population, as well as the ELT- and ROMI-switching subpopulations are summarized in Table 1. Median PC values over time are represented in Figure 1 for the Entire Population. For the Entire Population, after switching to AVA 20mg daily, there was an initial early increase in median PC from baseline noted on day 15, with median PC remaining well above 50 x10 9/L at each subsequent time point with less variability compared with day 15. ROMI-switched patients had a higher BL median PC than ELT-switchers (170 vs 76 x10 9/L).; median PC in patients switching from ELT rose from BL, whereas those switched from ROMI maintained a similar median PC throughout, with the minimum PC observed being similar to the minimum BL value (27 vs 24×10 9/L). Summary/Conclusion: In a population of patients who were generally responding to TPO-RAs prior to a switch to AVA, mean/median PCs were either improved or maintained with AVA treatment over 90 days. Importantly, patient satisfaction was also higher across each domain of the TSQM-9 with AVA treatment (convenience, global satisfaction, safety, and effectiveness) than with the prior TPO-RA (results reported in related abstract submission) suggesting that some patients may experience sustained effectiveness paired with enhanced overall treatment satisfaction when switching from ELT or ROMI.