Addy Grace, Scirocco Erica, Gelevski Dario, Rohrer Margot, Roderick Aimee, McCormack Mary, Weiss Sadan Anat, Scalia Jennifer, Parikh Neil, Giacomelli Elisa, Locatelli Matteo, Neel Dylan V, D'Agostino Derek, Leite Alex, Yu Hong, Sherman Alexander V, Mock Jarrad, Kalmes Andreas, Luppino Sarah, Babu Suma, Berry James, Cudkowicz Merit, Paganoni Sabrina
Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Revalesio, Tacoma, Washington, USA.
Muscle Nerve. 2025 Mar 21. doi: 10.1002/mus.28398.
RNS60 is an investigational product in clinical development for amyotrophic lateral sclerosis (ALS). RNS60 slowed disease progression in the ALS SOD1 mouse model and was safe and well tolerated both in an open-label pilot study and a randomized, placebo-controlled, multicenter phase 2 trial in people living with ALS. The objective of this ongoing expanded access protocol (EAP) was to provide RNS60 to people living with ALS who are ineligible for controlled clinical trials and to collect data on the safety and tolerability of dosing RNS60 via twice-daily nebulization rather than the previously studied daily nebulization with weekly intravenous administration.
Eligible participants (≥ 18 years old, diagnosed with ALS per investigator assessment, and ineligible for an ALS clinical trial testing RNS60) were treated with twice-daily nebulization of RNS60 at home. Safety was evaluated by the assessment of adverse events and routine safety labs.
A total of 84 participants have been treated with RNS60 via nebulization twice daily for up to 48 months so far. The most common treatment-related adverse event was increased secretions [N = 27 (32%)]. Serious adverse events (SAEs) [69 occurrences; N = 38 (45%) with at least one SAE] and deaths [N = 24 (28%)] were deemed not related to RNS60.
This EAP supports the benign side effect profile of RNS60 when administered via twice-daily nebulization and demonstrates the feasibility of long-term EAPs as a complementary approach to controlled trials in people with advanced ALS.
RNS60是一种正在进行临床开发用于治疗肌萎缩侧索硬化症（ALS）的研究性产品。在ALS超氧化物歧化酶1（SOD1）小鼠模型中，RNS60减缓了疾病进展，并且在一项开放标签的先导研究以及一项针对ALS患者的随机、安慰剂对照、多中心2期试验中均显示出安全且耐受性良好。这项正在进行的扩大准入方案（EAP）的目的是为不符合对照临床试验条件的ALS患者提供RNS60，并收集通过每日两次雾化吸入而非先前研究的每日雾化吸入加每周静脉给药方式给予RNS60的安全性和耐受性数据。
符合条件的参与者（年龄≥18岁，经研究者评估确诊为ALS，且不符合测试RNS60的ALS临床试验条件）在家中接受每日两次的RNS60雾化吸入治疗。通过评估不良事件和常规安全实验室指标来评价安全性。
截至目前，共有84名参与者接受了每日两次的RNS60雾化吸入治疗，最长达48个月。最常见的与治疗相关的不良事件是分泌物增多[N = 27（32%）]。严重不良事件（SAEs）[共69次发生；N = 38（45%）有至少一次SAE]和死亡事件[N = 24（28%）]被认为与RNS60无关。
该EAP支持每日两次雾化吸入给予RNS60时其良好的副作用特征，并证明了长期EAP作为晚期ALS患者对照试验补充方法的可行性。
