The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to tolebrutinib for the treatment of adults with non-relapsing secondary progressive multiple sclerosis (nrSPMS). This is based on positive results from the HERCULES phase 3 study, demonstrating that tolebrutinib delayed the time to onset of 6-month confirmed disability progression (CDP), by 31% compared to placebo (HR 0.69; 95% CI 0.55-0.88; p=0.0026), with further analysis of secondary endpoints demonstrating that the number of participants who experienced confirmed disability improvement was nearly double with tolebrutinib (10%) compared to those on placebo (5%) (HR 1.88; 95% CI 1.10 to 3.21; nominal p=0.021).

美国食品药品监督管理局 (FDA) 已授予托布替尼突破性疗法认定，用于治疗成人非复发性继发性进行性多发性硬化症 (nrSPMS)。这是基于 大力神 第 3 阶段研究表明，与安慰剂相比，托布替尼将 6 个月确认的残疾进展 (CDP) 的发病时间推迟了 31% (HR 0.69; 95% CI 0.55-0.88; p=0.0026)，对次要终点的进一步分析表明，使用托布替尼后确认残疾改善的参与者数量 (10%) 几乎是使用安慰剂的参与者数量的两倍 (5%) (HR 1.88; 95% CI 1.10 至 3.21; 名义 p=0.021)。

FDA Breakthrough Therapy designation is designed to expedite the development and review of medicines in the US that target serious or life-threatening conditions. Medicines qualifying for this designation must show preliminary clinical evidence that the drug may demonstrate substantial improvement on clinically significant endpoints over available medicines.

FDA 突破性疗法认定旨在加快美国针对严重或危及生命疾病的药物的开发和审查。符合此认定的药物必须提供初步临床证据，证明该药物在临床显著终点方面可能比现有药物有显著改善。

Erik Wallström, MD, PhD Global Head of Neurology Development, Sanofi “This Breakthrough Therapy designation demonstrates the potential for tolebrutinib to delay disability progression, a critical unmet need for people living with multiple sclerosis. We look forward to working with the FDA during the regulatory review of this first of its kind medicine in non-relapsing secondary progressive multiple sclerosis where there are currently no approved treatments available.”

Erik Wallström 医学博士、哲学博士赛诺菲神经学开发全球负责人：“这项突破性疗法认定表明托布替尼具有延缓残疾进展的潜力，这是多发性硬化症患者尚未满足的关键需求。我们期待与 FDA 合作，对这种首创药物进行监管审查，用于治疗非复发性继发性进行性多发性硬化症，目前尚无获批的治疗方法。”

Liver enzyme elevations (>3xULN) were observed in 4.1% of participants receiving tolebrutinib compared with 1.6% in the placebo group. A small (0.5%) proportion of participants in the tolebrutinib group experienced peak ALT increases of >20xULN, all occurring within the first 90 days of treatment. All but one case of liver enzyme elevations resolved without further medical intervention. The implementation of more frequent monitoring has helped mitigate serious liver sequelae.

接受托布替尼治疗的受试者中，4.1% 出现肝酶升高（>3xULN），而安慰剂组为 1.6%。托布替尼组中一小部分 (0.5%) 受试者的 ALT 峰值升高超过 20xULN，均发生在治疗的前 90 天内。除一例肝酶升高外，其余病例均在未进行进一步医疗干预的情况下得到缓解。实施更频繁的监测有助于减轻严重的肝脏后遗症。

Regulatory submissions of tolebrutinib are currently being finalized for the US and prepared for the EU. As with other medicines, Sanofi plans to confirm once a regulatory submission for tolebrutinib has been accepted. The PERSEUS phase 3 study in primary progressive MS is currently ongoing with study results anticipated in H2 2025.

托布替尼在美国的监管申请目前正在最后审定，欧盟的申请也正在准备中。与其他药物一样，赛诺菲计划在托布替尼的监管申请被接受后予以确认。PERSEUS 治疗原发性进展型 MS 的 3 期研究目前正在进行中，研究结果预计将于 2025 年下半年公布。

Tolebrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.

托鲁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。