Phase 3 ESLIM-01 study: Final analysis of efficacy and safety of long-term treatment with sovleplenib in adults with chronic primary immune thrombocytopenia

Abstract

Abstract Introduction Sovleplenib, a novel spleen tyrosine kinase (SYK) inhibitor, demonstrated promising safety and efficacy in primary immune thrombocytopenia (ITP) patients (pts) in phase 1b/2 trials, with these favorable outcomes subsequently confirmed in double-blinded phase 3 ESLIM-01 study (NCT05029635). This final analysis of ESLIM-01 sought to report the long-term efficacy and safety of sovleplenib in adult pts with ITP. Methods In ESLIM-01, adult pts with chronic primary ITP were randomized 2:1 to receive oral sovleplenib 300 mg once daily or placebo for 24 weeks. Pts who completed 24 weeks double-blinded treatment or demonstrating non-response within initial 12 weeks in ESLIM-01 were enrolled in an open-label extension sub-study (sovleplenib 300 mg once daily). Long-term efficacy and safety evaluations encompassed all participants who received ≥1 dose of sovleplenib (all Sov group), including placebo-crossover subjects (P-Sov group). Main efficacy endpoints included durable response in long-term follow up (PLT ≥ 50×10/L at ≥ 2 of 3 any 12-week consecutive protocol-defined visits after receiving sovleplenib for 12 weeks, not impacted by rescue treatment) and complete response rate (the proportion of pts with at least one PLT ≥100×10⁹/L under sovleplenib treatment, not impacted by rescue treatment). Results As of the March 31, 2025 data cutoff, 179 pts (all Sov) received at least one dose of sovleplenib treatment. Of these, 126 pts received sovleplenib initially during double-blinded period, while 53 pts (P-Sov) switched from placebo. The two groups were comparable in terms of baseline characteristics. At baseline, the median age in all Sov group was 43.0 years (range, 18.0-72.0) and 41.0 years (range, 18.0-69.0) in P-Sov group. The median platelet counts at baseline were 12.0×10⁹/L in both the all Sov and P-Sov groups. The proportion of pts who received concomitant anti-ITP medication at baseline was 30.7% in all Sov group and 26.4% in P-Sov group. 110 pts (61.5%) in all Sov group and 34 pts (64.2%) in P-Sov group achieved durable response in long-term follow up, respectively. The complete response rate was 67.6% in all Sov group and 68.0% in P-Sov group. The maximum continuous duration of PLT ≥ 50×10⁹/L (or≥ 30×10⁹/L) was 25.9 weeks (or 37.0 weeks) in all Sov group, and 20.4 weeks (or 35.6 weeks) in P-Sov group. Cumulative duration of PLT ≥ 50×10⁹/L (or≥ 30×10⁹/L) in all Sov group was 66.7 weeks (or 77.0 weeks) and 50.4 weeks (or 68.1 weeks) in P-Sov group. 16 pts (8.9%) reduced/discontinued concomitant anti-ITP medication in all Sov group and 5 pts (9.4%) in P-Sov group. The median duration (min, max) of exposure was 604.0 days (14.0, 1093.0) in all Sov group and 617.0 days (14.0, 1093.0) in P-Sov group. Treatment-related adverse events (TRAEs) were reported in 87.2% (156/179) of patients in all Sov group and 88.7% (47/53) in P-Sov group. The majority of AEs were Grade 1-2. The long-term safety profiles were consistent with those in sovleplenib group in ESLIM-01. The most common (>2.0%) TRAEs of grade ≥3 in all Sov group were alanine aminotransferase increased (4 [2.2%]), neutrophil count decreased (5 [2.8%]); for P-Sov group, it was aspartate aminotransferase increased (2 [3.8%]). Major bleeding events (ISTH criteria) occurred in 2.2% of all Sov group and 3.8% of P-Sov group. The study had no mortality events. Conclusions Long-term treatment with sovleplenib demonstrated clinically meaningful and sustained platelet responses in adult pts with ITP in China, while maintaining a tolerable safety profile. These findings support sovleplenib as a promising therapeutic option for adult pts with chronic primary ITP.Keywords: SYK, Immune thrombocytopenia (ITP), Sovleplenib, ESLIM-01