Long-Term Sovleplenib Treatment of Adults with Primary Immune Thrombocytopenia in China

Introduction Sovleplenib, a novel spleen tyrosine kinase (SYK) inhibitor, showed a clinically meaningful sustained platelet response with a tolerable safety profile in adults with immune thrombocytopenia (ITP) in a randomized, double-blind, placebo-controlled phase 3 study (ESLIM-01) in China1. Here we reported the long-term safety and efficacy data of ESLIM-01 extension stage in a follow-on, open-label sub-study (NCT05029635). Methods ESLIM-01 enrolled adults with chronic primary ITP who failed to ≥1 prior ITP treatment, and the mean platelet counts (PLT) < 30×10⁹/L at 3 screening visits. Eligible patients (pts) were randomized (2:1) to receive sovleplenib 300 mg orally once daily (QD), or placebo for 24 weeks (wks). Pts who completed 24 wks of treatment, or did not respond during the first 12 wks of treatment in ESLIM-01 could be enrolled in an open-label sub-study to receive sovleplenib 300mg QD treatment. The long-term safety and efficacy were assessed in all treated pts with at least one dose of sovleplenib (all Sov group), including the cross-over pts from placebo (P-Sov group). The main efficacy endpoint of durable response was defined as: PLT ≥50 × 10⁹/L at ≥4 of 6 scheduled visits during wks 14 to 24 in ESLIM-01 or, PLT ≥50×10⁹/L at ≥ 2 of 3 protocol-defined visits during the second 12 wks of 24 wks in the open-label sub-study. Long-term durable response was defined as after receiving sovleplenib for 12 wks, PLT ≥ 50×109/L at ≥ 2 of 3 any 12-week consecutive protocol-defined visits. Overall response was defined as at least one PLT ≥50 × 10⁹/L under sovleplenib treatment. Any PLT impacted by rescue therapy was not considered for efficacy endpoint derivation. Results At data cutoff date (Jan 31, 2024), a total of 179 pts (all Sov) were treated with at least one dose of sovleplenib. Among them, 126 pts initially received sovleplenib and 53 pts (P-Sov) initially received placebo in ESLIM-01. 99 (55.3%) of 179 pts in all Sov group, and 28 (52.8%) of 53 pts in P-Sov group were still on the treatment in the sub-study. The median duration (min, max) of exposure was 56.6 wks (2.0, 105.3) in all sov group and 52.3 wks (2.0, 102.9) in P-Sov group. Baseline characteristics were generally similar between the two groups. The median age was 43.0 years in all Sov group and 41.0 years in P-Sov group, median duration from the first PLT reduction to the first sovleplenib dose was 7.7 years in all Sov group and 8.0 years in P-Sov group, and pts in both groups had a median of 4.0 lines of prior medications for ITP, including 72.6% and 67.9% of patients who received prior TPO/TPO-RA treatment in all Sov group and P-Sov group, respectively. An overall response was achieved by 145 of 179 pts (81.0%) in all Sov group, and 44 of 53 pts (83.0%) in P-Sov group. 92 pts (51.4%) in all Sov group, and 23 pts (43.4%) in P-Sov group achieved durable response, respectively. The durable response rates were highly consistent with that in sovleplenib group (48%) in ESLIM-011. Long-term durable response rate was 59.8% in all Sov group and 64.2% in P-Sov group. The median cumulative duration of PLT ≥50 × 10⁹/L (or ≥30 × 10⁹/L) was 38.9 wks (or 48.2 wks) in all Sov group, and 35.1 wks (or 43.4 wks) in P-Sov group. 22.9% of pts in all Sov group and 18.9% of pts in P-Sov group received rescue therapy. Compared to the data in ESLIM-01 (22% of sovleplenib vs. 35% of placebo)1, long-term treatment did not increase the patient proportion for rescue therapy. The incidence of major bleeding events per ISTH criteria in all Sov group was 2.2%, consistent with that of sovleplenib group in ESLIM-01. The most frequent (>1.0%) TRAEs of grade 3 or higher in all Sov group were alanine aminotransferase increased (4 [2.2%]), neutrophil count decreased (3 [1.7%]), gamma-glutamyltransferase increased (3 [1.7%]), aspartate aminotransferase increased (2 [1.1%]), and hypertension (2 [1.1%]); for P-Sov group, they were 1 (1.9%), 0, 1 (1.9%), 2 (3.8%), and 0, respectively. There were no deaths in ESLIM-01 extension stage. Conclusions Long-term treatment with sovleplenib was effective in increasing and maintaining platelet count with well tolerated safety in adults with chronic primary ITP in China. No new safety signals were identified. Key words: sovleplenib, immune thrombocytopenia, ITP, SYK inhibitor, SYK References: Yu Hu, et al. Lancet Haematol. 2024 Jun 13: S2352-3026(24)00139-X.