The US Food and Drug Administration (FDA) is evaluating under priority review the regulatory submission of tolebrutinib to treat non-relapsing secondary progressive multiple sclerosis (nrSPMS) and to slow disability accumulation independent of relapse activity in adult patients. The target action date for the FDA decision is September 28, 2025. A regulatory submission is also under review in the EU.

美国食品药品监督管理局 (FDA) 正在优先审查托布替尼的监管申请，该药物用于治疗非复发性继发性进行性多发性硬化症 (nrSPMS) 并减缓成年患者中与复发活动无关的残疾积累。FDA 决定的目标行动日期是 2025 年 9 月 28 日。欧盟的监管申请也在接受审查。

from the phase 3 studies HERCULES in nrSPMS and GEMINI 1 and 2 in relapsing MS (RMS). The findings from these studies, as well as additional clinical and preclinical studies, support the differentiated mechanism of tolebrutinib to target disability progression independent of relapse activity, and the scientific hypothesis that smoldering neuroinflammation represents a key inflammatory process in MS and is a critical driver of disability accumulation..

来自3期研究HERCULES在nrSPMS和GEMINI 1和2在复发缓解型MS（RMS）中的结果。这些研究的发现，以及额外的临床和临床前研究，支持了tolebrutinib的独特作用机制，即独立于复发活动来针对残疾进展，并支持了这样的科学假设：持续的神经炎症是MS中的一个关键炎症过程，也是残疾积累的关键驱动因素。

Erik Wallström, MD, PhD

埃里克·瓦尔斯特罗姆，医学博士，哲学博士

Global Head of Neurology Development

全球神经学开发主管

“The totality of data across our clinical program validates our scientific understanding of smoldering neuroinflammation as a distinct inflammatory process in MS. People living with non-relapsing secondary progressive multiple sclerosis or who experience disability independent of relapse activity suffer from disability that worsens over time due to persistent inflammation in the brain, known as smoldering neuroinflammation, which is the primary driver of disability.

“我们临床项目中的全部数据验证了我们对隐匿性神经炎症作为一种多发性硬化症中独特炎症过程的科学理解。患有非复发性继发进展型多发性硬化症或经历与复发活动无关的残疾的患者，由于大脑中持续存在的炎症（称为隐匿性神经炎症）导致其残疾随着时间的推移而加重，这是残疾的主要驱动因素。”

The demonstrated ability of tolebrutinib to delay disability by targeting underlying drivers of the disease represents a potential paradigm shift in treating these patients.” .

托莱布替尼显示出通过针对疾病的根本驱动因素来延缓残疾的能力，这代表了治疗这些患者的潜在范式转变。"

Tolebrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority. The PERSEUS phase 3 study of tolebrutinib in patients with primary progressive MS is currently ongoing with study results anticipated in H2 2025.

Tolebrutinib 目前正在临床研究中，其安全性和有效性尚未得到任何监管机构的评估。Tolebrutinib 针对原发性进展型多发性硬化症（MS）患者的 PERSEUS 三期研究目前正在进行中，预计将于 2025 年下半年公布研究结果。

About multiple sclerosis

关于多发性硬化症

Multiple sclerosis is a chronic, immune-mediated, neurodegenerative disease that may result in accumulation of irreversible disabilities over time. The physical and cognitive disability impairments translate into gradual deterioration of health status, impacting patients’ care and quality of life. Disability accumulation remains the significant unmet medical need in MS.

多发性硬化症是一种慢性、免疫介导的神经退行性疾病，随着时间的推移可能导致不可逆残疾的累积。身体和认知障碍会逐渐恶化健康状况，影响患者的护理和生活质量。残疾累积仍然是多发性硬化症中亟待解决的重要医疗需求。

To date, the primary target of currently approved medicines has been peripheral B and T cells, while innate immunity within the CNS, which is believed to drive disability accumulation, remains largely unaddressed. Currently approved or late-stage medicines being tested for MS mainly target the adaptive immune system and/or do not act directly within the central nervous system to drive clinical benefit..

迄今为止，目前已批准药物的主要靶点是外周B细胞和T细胞，而中枢神经系统内的先天免疫——被认为驱动残疾积累——仍然在很大程度上未被解决。目前批准或处于后期测试阶段的多发性硬化症药物主要针对适应性免疫系统，和/或并非直接作用于中枢神经系统以带来临床益处。

Living with nrSPMS refers to people with MS who have stopped experiencing relapses but continue to accumulate disability, experienced as symptoms such as fatigue, cognitive impairment, balance and gait impairment, loss of bowel and/or bladder function, sexual disfunction, amongst others.

生活在nrSPMS中是指那些停止经历复发但继续累积残疾的多发性硬化症患者，这些残疾表现为疲劳、认知障碍、平衡和步态障碍、肠道和/或膀胱功能丧失、性功能障碍等症状。

About tolebrutinib

关于托勒布替尼

Tolebrutinib is an investigational, oral, brain-penetrant, and bioactive Bruton’s tyrosine kinase (BTK) inhibitor specifically designed to target smoldering neuroinflammation, a key driver of disability progression in MS. Unlike currently approved MS therapies that primarily address peripheral inflammation, tolebrutinib uniquely crosses the blood-brain barrier to achieve therapeutic cerebrospinal fluid concentrations, allowing it to modulate B-lymphocytes and disease-associated microglia within the CNS.

托莱布替尼是一种研究性的、口服的、可穿透大脑的、具有生物活性的布鲁顿酪氨酸激酶（BTK）抑制剂，专门设计用于针对隐匿性神经炎症，这是多发性硬化症（MS）致残进展的关键驱动因素。与目前获批的主要针对外周炎症的多发性硬化症疗法不同，托莱布替尼能够独特地跨越血脑屏障，达到治疗性的脑脊液浓度，从而调节中枢神经系统内的B淋巴细胞和与疾病相关的小胶质细胞。

This mechanism is believed to address the underlying pathology of progressive MS by targeting the inflammatory processes that contribute to neurodegeneration and disability accumulation. .

该机制被认为通过针对导致神经退行性变和残疾累积的炎症过程，来解决进展型多发性硬化症的根本病理。

Tolebrutinib is being evaluated in phase 3 clinical studies for the treatment of various forms of multiple sclerosis and its safety and efficacy have not been evaluated by any regulatory authority worldwide. For more information on tolebrutinib clinical studies, please visit

托勒布替尼正在接受针对治疗多发性硬化症不同形式的第三阶段临床研究评估，其安全性和有效性尚未得到全球任何监管机构的评估。如需更多关于托勒布替尼临床研究的信息，请访问

About HERCULES

关于大力神

HERCULES (clinical study identifier: NCT04411641) was a double-blind randomized phase 3 clinical study evaluating the efficacy and safety of tolebrutinib in patients with nrSPMS. At baseline, nrSPMS was defined as having a SPMS diagnosis with an expanded disability status scale (EDSS) between 3.0 and 6.5, no clinical relapses for the previous 24 months and documented evidence of disability accumulation in the previous 12 months.

HERCULES（临床研究标识符：NCT04411641）是一项双盲随机的3期临床研究，评估了tolebrutinib在nrSPMS患者中的疗效和安全性。在基线时，nrSPMS被定义为SPMS诊断且扩展残疾状态量表（EDSS）评分在3.0至6.5之间，过去24个月无临床复发，并在过去12个月内有明确的残疾累积证据。

Participants were randomized (2:1) to receive either an oral daily dose of tolebrutinib or matching placebo for up to approximately 48 months..

参与者被随机分配（2:1）接受口服每日剂量的tolebrutinib或相匹配的安慰剂，持续约48个月。

The primary endpoint was 6-month CDP defined as the increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.0, or the increase of ≥0.5 point when the baseline EDSS score was >5.0. Secondary endpoints included time to onset of 3-month CDP as assessed by EDSS score, total number of new or enlarging T2 hyperintense lesions as detected by MRI, time to onset of confirmed disability improvement, 3-month change in 9-hole peg test and T25-FW test as well as the safety and tolerability of tolebrutinib..

主要终点是6个月的CDP，定义为当基线EDSS评分≤5.0时，相较于基线EDSS评分增加≥1.0分；或当基线EDSS评分>5.0时，增加≥0.5分。次要终点包括通过EDSS评分评估的3个月CDP发作时间、MRI检测到的新发或扩大的T2高信号病灶总数、确认的残疾改善发作时间、9孔插钉测试和T25-FW测试的3个月变化，以及tolebrutinib的安全性和耐受性。

About GEMINI 1 and 2

关于GEMINI 1和2

GEMINI 1 (clinical study identifier: NCT04410978) and GEMINI 2 (clinical study identifier: NCT04410991) were double-blind randomized phase 3 clinical studies evaluating the efficacy and safety of tolebrutinib compared to teriflunomide in patients with RMS. Participants were randomized in both studies (1:1) to receive either tolebrutinib and placebo daily or 14mg teriflunomide and placebo..

GEMINI 1（临床研究标识符：NCT04410978）和 GEMINI 2（临床研究标识符：NCT04410991）是双盲随机的三期临床研究，评估了tolebrutinib与特立氟胺在RMS患者中的疗效和安全性。在这两项研究中，参与者被随机分配（1:1），分别每日接受tolebrutinib加安慰剂或14毫克特立氟胺加安慰剂。

The primary endpoint for both studies was the annualized relapse rate for up to approximately 36 months defined as the number of confirmed adjudicated protocol defined relapses. Secondary endpoints included time to onset of CDW, confirmed over at least 6 months, defined as an increase of ≥1.5 points from the baseline EDSS score when the baseline score is 0, an increase of ≥1.0 point from the baseline EDSS score when the baseline score is 0.5 to ≤5.5 or an increase of ≥0.5 point from the baseline EDSS score when the baseline score was >5.5 in addition to the total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from baseline through the end of study, the total number of Gd-enhancing T1 hyperintense lesions as detected by MRI from baseline through the end of study and the safety and tolerability of tolebrutinib..

两项研究的主要终点均为年化复发率，定义为在约36个月内经确认的、符合方案规定的复发次数。次要终点包括确诊持续至少6个月的CDW（确诊残疾恶化）发生时间，定义为基线EDSS评分为0时增加≥1.5分，基线EDSS评分为0.5至≤5.5时增加≥1.0分，或基线EDSS评分>5.5时增加≥0.5分；此外还包括从基线到研究结束期间通过MRI检测到的新发和/或扩大的T2高信号病灶总数、从基线到研究结束期间通过MRI检测到的Gd增强T1高信号病灶总数，以及tolebrutinib的安全性和耐受性。

About Sanofi

关于赛诺菲

We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions..

我们是一家创新的全球医疗保健公司，由一个宗旨驱动：我们追寻科学的奇迹以改善人们的生活。我们的团队遍布全球，致力于通过努力将不可能变为可能来改变医学实践。我们为全球数百万人提供可能改变生命的治疗选择和拯救生命的重要疫苗保护，同时将可持续发展和社会责任置于我们目标的核心。

Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY

赛诺菲在EURONEXT上市，代码为SAN，在NASDAQ上市，代码为SNY。