Integrated analysis of the ropeginterferon alfa-2b clinical program in essential thrombocythemia to demonstrate molecular and hematologic responses with safety profile information across treatment lines, ethnicities, and driver mutation types.

Abstract

6576 Background: Patients with essential thrombocythemia (ET) have limited disease-modifying options. This integrated analysis of 182 ET patients from 2 trials evaluated consistency the efficacy of ropeginterferon alfa-2b (ropeg, BESREMi) across treatment lines and examined the impact of ethnicity and molecular subtype on outcomes. Methods: Data were pooled from the phase 3 randomized SURPASS-ET study (ropeg vs anagrelide [ANA] in HU-resistant/intolerant high-risk ET) and the phase 2b single-arm EXCEED-ET study enrolling both treatment-naïve and previously treated patients in North America. Endpoints included durable modified ELN response, hematologic and molecular responses, thrombotic events, and safety. Results: In SURPASS-ET, ropeg achieved a significantly higher durable modified ELN response at months 9 and 12 than ANA (42.9% vs 6.0%; p<0.0001), with superior platelet and WBC control, greater JAK2 V617F allelic burden reduction, and fewer major thrombotic events. In EXCEED-ET, durable objective modified ELN responses reached 60.2%, with ELN2009 molecular response rates of 35.0% for JAK2 V617F, 16.0% for CALR , and 25.0% for MPL, demonstrating consistent efficacy across treatment lines and mutation subtypes (Table 1). Safety profiles were comparable between studies, with mostly low-grade, manageable AEs. In the integrated analysis across studies, grade ≥3 TEAEs occurred in 28.6% of ropeg recipients and 33.8% of ANA. TEAEs leading to discontinuation (8.8% vs 20.0%) and serious AEs (12.6% vs 30.0%) were less frequent in the ropeg group. Fatal AEs occurred only in the ANA group (3.8%). Conclusions: Across the two studies, consistent molecular and hematologic efficacy with a favorable and manageable safety profile was demonstrated in treatment-naïve and pretreated ET populations, across ethnicities and disease drivers. These findings support ropeg as a disease-modifying treatment option with a favorable benefit–risk profile for all ET patients regardless of ethnicity, treatment line, driver mutation status, and mutational complexity. Clinical trial information: NCT04285086 , NCT05482971 . Key efficacy outcomes from both trials. Outcome SURPASS-ET EXCEED-ET RopegN=91 ANAN=83 RopegN=91 Durable modified ELN response, % Subgroup analysis by race, % (n)CaucasianAsianAfrican AmericanHispanicOther 42.920 (1/5)44.2 (38/86)--- 6.00 (0/2)6.2 (5/81)--- 60.257.2 (41/71)53.0 (4/7)100.0 (5/5)66.7 (2/3)100.0 (5/5) Platelet control ≤400×10⁹/L, % 56.0 21.7 48.4 WBC normalization, % 73.6 13.3 48.4 Molecular response*, % (n) JAK2 V617F 30.6 (19/62) 0 (0/42) 35.0 (7/20) CALR 30.0 (3/10) 0 (0/4) 16.0 (4/25) MPL 0 (0/1) 0 (0/1) 25.0 (2/8) Major thrombotic events, % 1.1 10.0 1.1 *The molecular response per the 2009 ELN criteria includes complete and partial responses.