Sanofi's oral BTK inhibitor tolebrutinib is heading towards an FDA decision in September as a potential treatment for multiple sclerosis (MS) after a priority review by the US regulator.

赛诺菲的口服BTK抑制剂tolebrutinib在获得美国监管机构的优先审查后，正朝着9月迎来FDA关于其作为多发性硬化症（MS）潜在治疗方案的决定。

Tolebrutinib is vying to become the first brain-penetrant BTK inhibitor to both treat non-relapsing secondary progressive MS (nrSPMS) and to slow the progression of disability caused by the disease, independent of relapse activity.

托莱布替尼有望成为首个可穿透大脑的BTK抑制剂，用于治疗非复发性继发进展型多发性硬化症（nrSPMS），并减缓该疾病导致的残疾进展，且独立于复发活动之外。

The FDA review – which is due to be completed by 28th September – revolves around the results of the

FDA的审查——定于9月28日完成——围绕着

HERCULES

赫拉克勒斯

trial which showed that tolebrutinib was able to delay the time to six-month disability progression by 31% compared to placebo in patients with nrSPMS. It has been awarded breakthrough status for this indication.

试验显示，与安慰剂相比，tolebrutinib 能够将 nrSPMS 患者六个月残疾进展的时间延迟 31%。它已被授予这一适应症的突破性地位。

Sanofi's decision to file for nrSPMS only comes after tolebrutinib failed to achieve its primary objective in two other phase 3 trials – GEMINI 1 and 2 – that involved patients with relapsing forms of MS.

赛诺菲决定仅针对nrSPMS提交申请，此前托莱布替尼在另外两项涉及复发性多发性硬化症患者的三期试验——GEMINI 1和2中未能达到其主要目标。

Treatment options for progressive MS are more limited, however, and Sanofi is hoping that tolebrutinib can become the first medicine to target so-called 'smouldering' neuroinflammation. While relapsing forms are characterised by sudden attacks associated with advancing disability, in non-relapsing patients the decline tends to be more continuous and driven by underlying nerve inflammation..

治疗进展型多发性硬化症的选择更为有限，然而赛诺菲希望tolebrutinib能够成为首个针对所谓“隐匿性”神经炎症的药物。虽然复发形式的特点是伴随失能加重的突发性发作，但在非复发患者中，病情的恶化往往更加持续，并由潜在的神经炎症所驱动。

Data from the GEMINI studies will be used to support the application for nrSPMS, while a fourth phase 3 trial called PERSEUS in patients with primary progressive MS (PPMS) is still ongoing, with results due in the second half of this year.

GEMINI 研究的数据将用于支持 nrSPMS 的申请，而名为 PERSEUS 的第四项针对原发性进展型多发性硬化症 (PPMS) 患者的 3 期试验仍在进行中，结果预计在今年下半年公布。

'The demonstrated ability of tolebrutinib to delay disability by targeting underlying drivers of the disease represents a potential paradigm shift in treating these patients,' commented Erik Wallström, Sanofi's global head of neurology development.

“托莱布替尼通过针对疾病的根本驱动因素来延缓残疾的能力，代表了治疗这些患者的潜在范式转变，”赛诺菲全球神经学开发主管埃里克·瓦尔斯特伦评论道。

Tolebrutinib was one of three oral BTK inhibitors that Sanofi acquired as part of its $3.7 billion buyout of

Tolebrutinib是赛诺菲以37亿美元收购的三种口服BTK抑制剂之一，

Principia Biopharma

原理生物制药公司

in 2020, and was abandoned as a treatment for

在2020年，并被弃用作治疗手段

myasthenia gravis

重症肌无力

- another neuromuscular disorder – in 2023 for what the company said were commercial reasons.

- 另一种神经肌肉疾病 - 公司称出于商业原因，于2023年停止相关工作。

The candidate is one of several oral BTK drugs that have been in clinical development for MS, including Merck KGaA's

该候选药物是多个处于多发性硬化症临床开发阶段的口服BTK药物之一，其中包括默克KGaA的药物。

evobrutinib

艾伏布替尼

– which failed two phase 3 trials and was abandoned for MS – as well as Roche's

——该药物在两项三期试验中失败并被放弃用于MS治疗——以及罗氏的

fenebrutinib

非尼布替尼

, Novartis' remibrutinib, and InnoCare Pharma's orelabrutinib.

，诺华的雷米鲁替尼和InnoCare Pharma的奥雷巴替尼。

Among the others, fenebrutinib is in phase 3 for PPMS, with results due in 2026, while remibrutinib is in phase 3 for relapsing MS and orelabrutinib generated positive results in relapsing-remitting forms of the disease that were presented at the ACTRIMS congress in February.

其中，fenebrutinib 正在进行 PPMS 的第三阶段试验，预计结果将在 2026 年发布；而 remibrutinib 正在进行复发性 MS 的第三阶段试验，orelabrutinib 在复发缓解型疾病形式中产生了积极的结果，并于 2 月在 ACTRIMS 大会上公布。

GlobalData has predicted that tolebrutinib will be the leading BTK inhibitor for MS by 2030, with forecasted sales of approximately $2.6 billion across seven of the largest pharma markets.

GlobalData 预测，到 2030 年，tolebrutinib 将成为多发性硬化症（MS）领域的领先 BTK 抑制剂，在七大制药市场中的销售额预计将达到约 26 亿美元。

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