Sovleplenib in patients with primary or secondary warm autoimmune haemolytic anaemia: results from phase 2 of a randomised, double-blind, placebo-controlled, phase 2/3 study.

This study aimed to assess the preliminary efficacy and safety of sovleplenib-an oral spleen tyrosine kinase inhibitor-in patients with warm autoimmune haemolytic anaemia in China.

本研究旨在评估中国温抗体型自身免疫性溶血性贫血患者口服脾酪氨酸激酶抑制剂sovleplenib的初步疗效和安全性。

Here we report on the phase 2 results.

这里我们报告了第二阶段的研究结果。

Methods

This randomised, double-blind, placebo-controlled, phase 2 part from the phase 2/3 study was conducted at 13 centres in China.

这项随机、双盲、安慰剂对照的第二阶段研究，作为第二/第三阶段研究的一部分，在中国13个中心进行。

Eligible patients, aged 18-75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of no more than 2, had primary or secondary warm autoimmune haemolytic anaemia (stable underlying disease not requiring drug intervention) with no response to previous glucocorticoid treatment, haemoglobin of less than 100 g/L with active haemolysis, and a positive direct antiglobulin test.

符合条件的患者年龄在18-75岁之间，东部肿瘤协作组（ECOG）表现状态不超过2级，患有原发性或继发性温抗体型自身免疫性溶血性贫血（稳定的基础疾病不需要药物干预），对之前的糖皮质激素治疗无反应，血红蛋白低于100 g/L且有活跃的溶血现象，并且直接抗球蛋白试验结果为阳性。

The study comprised two periods; patients were randomly assigned (3:1) to receive sovleplenib or placebo at 300 mg orally once a day in the 8-week double-blindperiod.

该研究包括两个阶段；患者被随机分配（3:1）在8周的双盲期间每天一次口服300 mg的sovleplenib或安慰剂。

Upon completion, all patients entered an open-label treatment period for at least 16 weeks and received sovleplenib 300 mg once a day until 24 weeks after the last patient was randomly assigned.

完成试验后，所有患者进入至少16周的开放标签治疗期，并接受每天一次的300 mg sovleplenib治疗，直到最后一名患者随机分配后的第24周。

The primary endpoint for phase 2 of the trial was overall haemoglobin response rate (haemoglobin ≥100 g/L with an increase of ≥20 g/L from baseline at least once, and haemoglobin not affected by rescue therapy, such as red blood cell transfusions, intravenous immunoglobulin, and glucocorticoids) by week 24.

试验第二阶段的主要终点是第24周时的总血红蛋白反应率（血红蛋白≥100 g/L，至少一次从基线增加≥20 g/L，并且血红蛋白不受救援治疗如红细胞输血、静脉注射免疫球蛋白和糖皮质激素的影响）。

Efficacy analyses in the 0-8 week double-blindperiod included all patients who were randomly assigned, analysed by intention-to-treat.

0-8周双盲期的疗效分析包括了所有被随机分配并按意向治疗分析的患者。

Safety analysis in the double-blindperiod included patients in the intention-to-treatpopulation who received at least one dose of the study medication.

双盲期的安全性分析包括了意向治疗人群中至少接受了一次研究药物治疗的患者。

This phase 2/3 study is registered with ClinicalTrials.gov, NCT05535933, and the phase 3 part is ongoing.

这项2/3期研究已在ClinicalTrials.gov注册，编号为NCT05535933，其中3期部分正在进行中。

Results

Between Sept 26, 2022, and May 9, 2023, 34 patients were screened and 21 patients (four [19%] male and 17 [81%] female) were enrolled in the study and randomly assigned to receive either sovleplenib (n=16) or placebo (n=5).

在2022年9月26日至2023年5月9日期间，共有34名患者接受了筛查，其中21名患者（男性4名[19%]，女性17名[81%]）被纳入研究，并随机分配接受sovleplenib（n=16）或安慰剂（n=5）。

All 21 patients completed the 0-8-week double-blindtreatment and entered the open-label treatment period.

所有21名患者完成了0-8周的双盲治疗，并进入了开放标签治疗期。

The overall haemoglobin response rate was 67% (14 of 21 patients) by week 24, and durable haemoglobin response rate was 48% (ten of 21 patients) by week 24.

到第24周时，总体血红蛋白反应率为67%（21名患者中有14名），持续的血红蛋白反应率为48%（21名患者中有10名）。

During the 0-8-week double-blindtreatment, 13 (81%) of 16 patients in the sovleplenib group versus five (100%) of five patients taking placebo reported treatment-emergent adverse events (TEAEs), and four (25%) of 16 patients versus four (80%) of five patients reported grade 3 adverse events.

在0-8周的双盲治疗期间，16名接受sovleplenib治疗的患者中有13名（81%）报告了治疗相关不良事件（TEAEs），而接受安慰剂的5名患者中有5名（100%）报告了TEAEs；16名患者中有4名（25%）报告了3级不良事件，而5名患者中有4名（80%）报告了3级不良事件。

Although all 21 patients had a TEAE during the 24-week treatment with sovleplenib, only seven (33%) patients had grade 3 events.

尽管所有21名患者在24周的sovleplenib治疗期间都出现了TEAEs，但只有7名（33%）患者出现了3级事件。

The most common grade 3 TEAE was anaemia (four [19%] patients), which was not related to treatment.

最常见的3级治疗相关不良事件是贫血（四名[19%]患者），这与治疗无关。

There were no grade 4 or 5 TEAEs.

没有4级或5级的治疗相关不良事件。

interpretation

Sovleplenib treatment achieved an encouraging overall haemoglobin response in Chinese patients with warm autoimmune haemolytic anaemia and was well tolerated.

Sovleplenib治疗在患有温抗体型自身免疫性溶血性贫血的中国患者中取得了令人鼓舞的总血红蛋白反应，并且耐受性良好。

The phase 3 part of the study (ESLIM-02) is currently ongoing to further substantiate the efficacy and safety of sovleplenib in this setting.

该研究的第三阶段（ESLIM-02）目前正在继续进行，以进一步证实sovleplenib在此情况下的疗效和安全性。

funding

HUTCHMED.

和记黄埔医药