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2558 Long-Term Sovleplenib Treatment of Adults with Primary Immune Thrombocytopenia in China

Program: Oral and Poster Abstracts
Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Yu Hu1*, Renchi Yang, MD2, Xiaofan Liu, MD2*, Heng Mei, md, phd3*, Hu Zhou4, Shujie Wang5*, Ruibin Huang, MD6*, Yi Wang7*, Xin Du8*, Jing Sun9*, Zeping Zhou10*, Zhenyu Yan11*, Wenming Chen12*, Wei Wang13*, Qingchi Liu14*, Qingshu Zeng15*, Yuping Gong16*, Jie Yin17*, Xuliang Shen18*, Baodong Ye19*, Yun Chen20*, Yajing Xu, MD21*, Huiping Sun22*, Yunfeng Cheng23, Zhuogang Liu24*, Chunling Wang, PhD25*, Guolin Yuan26*, Xiaohui Zhang27, Xin Li28*, Peng Cheng29*, Xinhong Guo30*, Zhongxing Jiang31*, Feng'e Yang32*, Linhua Yang33*, Chengwei Luo Luo, M.D.34*, Taiwu Xiao35*, Hongyan Yin36*, Xiaojun Guo36*, Xian Luo36*, Songhua Fan36*, Michael M. Shi36* and Weiguo Su36*

1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
3Union Hospital, Tongji Medical College, HUST, Wuhan, China
4Department of Hematology, Henan Provincial Cancer Hospital, Zhengzhou, China
5Peking Union Medical College Hospital, Beijing, China
6The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
7Shaanxi Provincial People's Hospital, Xi'an, China
8Department of Hematology and Shenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
9Nanfang Hospital Southern Medical University, Guangzhou, China
10Second Affiliated Hospital of Kunming Medical University, Kunming, China
11North China University of Science and Technology Affiliated Hospital, Tangshan, China
12Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China
13The Affiliated Hospital of Qingdao University, Qingdao, China
14The First Hospital of Hebei Medical University, Shijiazhuang, China
15Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
16West China Hospital of Sichuan University, Chengdu, China
17First Affiliated Hospital of Soochow University, Suzhou, China
18Heping Hospital Affiliated To Changzhi Medical College, Changzhi, China
19The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
20Central Hospital Affiliated to Shandong First Medical University, Jinan, China
21Xiangya Hospital, Central South University, Changsha, Hunan, China
22Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
23Jinshan Hospital of Fudan University, Shanghai, China
24Shengjing Hospital of China Medical University, Shenyang, China
25Department of Hematology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai'an, China
26Xiangyang Central Hospital, Xiangyang, China
27Peking University People's Hospital, Beijing, China
28Department of Hematology, Third Xiangya Hospital of Central South University, Changsha, China
29The First Affiliated Hospital of Guangxi Medical University, Nanning, China
30The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
31The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
32Fujian Medical University Union Hospital, Fuzhou, China
33The Second Hospital of Shanxi Medical University, Taiyuan, China
34Department of Hematology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
35Liaocheng People's hospital, Liaocheng, CHN
36HUTCHMED Limited, Shanghai, 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:

  1. Yu Hu, et al. Lancet Haematol. 2024 Jun 13: S2352-3026(24)00139-X.

Disclosures: Yin: HUTCHMED Limited: Current Employment. Guo: HUTCHMED Limited: Current Employment. Luo: HUTCHMED Limited: Current Employment. Fan: HUTCHMED Limited: Current Employment. Shi: HUTCHMED Limited: Current Employment. Su: HUTCHMED Limited: Current Employment.

*signifies non-member of ASH