Positive results from the HERCULES phase 3 study showed that tolebrutinib, Sanofi’s oral brain-penetrant BTK inhibitor, met the primary endpoint of improvement over placebo in delaying time to onset of confirmed disability progression (CDP) in people with non-relapsing secondary progressive MS (nrSPMS). In the HERCULES study, nrSPMS was defined at baseline as having a SPMS diagnosis with an expanded disability status scale (EDSS) score 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. Preliminary analysis of liver safety was consistent with previous tolebrutinib studies.

HERCULES 3 期研究的积极结果表明，赛诺菲的口服脑渗透性 BTK 抑制剂托布替尼在延迟非复发性继发性进展型 MS (nrSPMS) 患者确诊残疾进展 (CDP) 的时间方面优于安慰剂，达到了主要终点。在 HERCULES 研究中，nrSPMS 在基线时被定义为患有 SPMS 且扩展残疾状态量表 (EDSS) 评分在 3.0 至 6.5 之间，过去 24 个月内没有临床复发，并且有记录证明过去 12 个月内残疾积累。肝脏安全性的初步分析与之前的托布替尼研究一致。

Results from the GEMINI 1 and 2 phase 3 studies evaluating tolebrutinib did not meet the primary endpoint of reducing annualized relapse rate (ARR), compared to teriflunomide, in people with relapsing forms of multiple sclerosis. However, analysis of the key secondary endpoint of pooled 6-month CDW data showed a considerable delay in time to onset, which supports the CDP data observed in HERCULES.

GEMINI 1 和 2 的 3 期临床试验结果显示，与特立氟胺相比，托布替尼未能达到降低复发型多发性硬化症患者的年复发率 (ARR) 的主要终点。然而，对汇总的 6 个月 CDW 数据的关键次要终点的分析显示，发病时间明显延迟，这支持了 HERCULES 中观察到的 CDP 数据。

Houman Ashrafian, MD, PhD Head of Research & Development, Sanofi“Tolebrutinib represents an unprecedented breakthrough as a potential first-in-disease treatment option with clinically meaningful benefit in disability accumulation. Addressing disability accumulation, thought to be driven by smoldering neuroinflammation, remains the greatest unmet medical need in people with non-relapsing secondary progressive MS today.”

赛诺菲研发主管Houman Ashrafian 医学博士“托布替尼代表了前所未有的突破，它是一种潜在的首个疾病治疗选择，在残疾积累方面具有临床意义。治疗残疾积累被认为是由阴燃性神经炎症驱动的，目前仍然是非复发性继发性进展型 MS 患者最大的未满足医疗需求。”

The PERSEUS phase 3 study in primary progressive MS, evaluating time to onset of CDP, is currently ongoing with study results anticipated in 2025.

PERSEUS 针对原发进展型 MS 的 3 期研究目前正在进行中，该研究旨在评估 CDP 的发病时间，预计研究结果将于 2025 年公布。

Study results for HERCULES and GEMINI 1 and 2 will be presented at the upcoming European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) medical meeting in Copenhagen, Denmark, September 20, 2024. Tolebrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.

HERCULES 和 GEMINI 1 和 2 的研究结果将于 2024 年 9 月 20 日在丹麦哥本哈根举行的欧洲多发性硬化症治疗和研究委员会 (ECTRIMS) 医学会议上公布。托布替尼目前正在进行临床研究，其安全性和有效性尚未经过任何监管机构的评估。

Multiple sclerosis is a chronic, immune-mediated, neurodegenerative disease that results in accumulation of irreversible disabilities over time. The physical and cognitive disability impairments translate into gradual deterioration of health status and lower quality of life, impacting patients’ care and life expectancy.

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，会导致不可逆转的残疾。身体和认知障碍导致健康状况逐渐恶化，生活质量下降，影响患者的护理和预期寿命。

Disability accumulation remains the significant unmet medical need in MS. To date, the primary target of current therapies has been peripheral B and T cells, while innate immunity, which is believed to drive disability accumulation, remains largely unaddressed by current therapies. Currently approved or medicines being tested for MS mainly target the adaptive immune system and/or do not act directly within the central nervous system (CNS) to drive clinical benefit.​

残疾累积仍然是 MS 中未得到满足的重要医疗需求。迄今为止，当前疗法的主要目标是外周 B 细胞和 T 细胞，而先天免疫被认为是导致残疾累积的原因，而目前的疗法在很大程度上仍未解决这一问题。目前已获批或正在测试的 MS 药物主要针对适应性免疫系统和/或不直接作用于中枢神经系统 (CNS) 以产生临床益处。​

RMS refers to people with MS who experience episodes of new or worsening symptoms (known as relapses) followed by periods of partial or complete recovery. nrSPMS refers to people with MS who have stopped experiencing confirmed relapses but continue to experience accumulation of disability, experienced as symptoms such as fatigue, cognition impairment, balance and gait impairment, loss of bowel and/or bladder function, sexual disfunction, amongst others.

RMS 指的是 MS 患者出现新的症状或症状恶化（称为复发），随后经历一段部分或完全康复期。nrSPMS 指的是 MS 患者已不再经历确诊的复发，但继续经历残疾的累积，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。

Tolebrutinib's mechanism of action modulates both B lymphocytes and activated microglia in the CNS, which is understood to address the underlying mechanisms of disability accumulation in MS linked to smoldering neuroinflammation in the brain and spinal cord.

托鲁替尼的作用机制是调节中枢神经系统中的 B 淋巴细胞和活化的小胶质细胞，这被认为可以解决与大脑和脊髓中阴燃的神经炎症相关的多发性硬化症中残疾积累的潜在机制。