The US 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

美国食品药品监督管理局（FDA）正在优先审查托莱布替尼的监管提交，用于治疗非复发性继发进展型多发性硬化症（nrSPMS），并减缓成年患者与复发活动无关的残疾累积。

The target action date for the FDA decision is September 28, 2025. A regulatory submission is also under review in the EU.

FDA 决策的目标行动日期是 2025 年 9 月 28 日。欧盟也在审查一项监管提交。

The regulatory submissions in the US and the EU are supported by the

美国和欧盟的监管提交得到了支持。

results

结果

from the phase III 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III期研究HERCULES在nrSPMS和GEMINI 1和2在复发缓解型MS（RMS）中的研究。这些研究的结果，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 Global Head of Neurology Development: “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.

埃里克·瓦尔斯特罗姆，医学博士，全球神经病学开发主管：“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恶化的患者，由于大脑中持续存在的炎症，即所谓的隐匿性神经炎症，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.”.

托莱布替尼证明了其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 III study of tolebrutinib in patients with primary progressive MS is currently ongoing with study results anticipated in H2 2025.

托莱布替尼目前正处于临床研究阶段，其安全性和有效性尚未得到任何监管机构的评估。托莱布替尼针对原发性进展型多发性硬化症患者的PERSEUS III期研究目前正在进行中，预计研究结果将于2025年下半年公布。

HERCULES (clinical study identifier: NCT04411641) was a double-blind randomized phase III 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III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被定义为具有SPMS诊断，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个月中有残疾积累的文件证据。

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

参与者被随机分配（2:1）接受口服每日剂量的托莱布替尼或匹配的安慰剂，持续约48个月。主要终点是6个月CDP，定义为当基线EDSS评分≤5.0时，从基线EDSS评分增加≥1.0分；或当基线EDSS评分>5.0时，增加≥0.5分。

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..

次要终点包括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、确认残疾改善的发作时间、9孔插板试验和T25-FW试验的3个月变化，以及tolebrutinib的安全性和耐受性。

GEMINI 1 (clinical study identifier: NCT04410978) and GEMINI 2 (clinical study identifier: NCT04410991) were double-blind randomized phase III 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III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。两项研究的参与者均被随机分配（1:1），接受每日一次tolebrutinib和安慰剂或14mg特立氟胺和安慰剂。

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，定义为经确认的、符合方案规定的复发次数，持续时间约为36个月。次要终点包括CDW（持续残疾恶化）发生的时间，在至少6个月内确认，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，以及托莱布替尼的安全性和耐受性。

Condition:

条件：

Multiple Sclerosis

多发性硬化症

Type:

类型：

drug

药物