Forrest Bruce D, Goyal Namita A, Fleming Thomas R, Bracci Paige M, Brett Neil R, Khan Zaeem, Robinson Michelle, Azhir Ari, McGrath Michael
Hudson Innovations, LLC, Nyack, NY 10960, USA.
Neuvivo, Inc., Palo Alto, CA 94301, USA.
Biomedicines. 2024 Oct 16;12(10):2367. doi: 10.3390/biomedicines12102367.
BACKGROUND/OBJECTIVES: The aim of this study was to estimate the effect of a 6 months' treatment course of the innate immune modulator NP001 (a pH-adjusted intravenous formulation of purified sodium chlorite), on disease progression, as measured by overall survival (OS) in patients with amyotrophic lateral sclerosis.
Blinded survival data were retrospectively collected for 268 of the 273 patients who had participated in two phase 2 placebo-controlled clinical trials of NP001 (ClinicalTrials.gov: NCT01281631 and NCT02794857) and received at least one dose of either 1 mg/kg or 2 mg/kg of NP001 as chlorite based on actual body weight, or placebo. Kaplan-Meier methods were used on the intent-to-treat population to estimate survival probabilities.
In the overall population, the median OS was 4.8 months (2.7 years [95% CI: 2.3, 3.5] in the 2 mg/kg NP001group and 2.3 years [95% CI: 1.8, 2.9] in the placebo group). Hazard ratio (HR): 0.77 (95% CI: 0.57, 1.03), = 0.073. Among patients aged ≤ 65 years, the median OS for the 2 mg/kg NP001 group was 10.8 months (3.3 years [95% CI: 2.4, 3.8] in the 2 mg/kg NP001 group and 2.4 years [95% CI: 1.7, 3.3] in the placebo group). HR: 0.69 (95% CI: 0.50, 0.95). No differences were observed in the 1 mg/kg NP001 group or in patients aged > 65 years.
The findings from this study suggest that a 6 months' treatment course of NP001 resulted in a 4.8-month increase in overall survival in patients with ALS. The findings from this study indicate that targeting inflammation associated with the innate immune system may provide a pathway for new therapeutic options for the treatment of ALS.
背景/目的：本研究旨在评估先天性免疫调节剂NP001（一种经pH调节的纯化亚氯酸钠静脉制剂）为期6个月的治疗疗程对肌萎缩侧索硬化症患者疾病进展的影响，以总生存期（OS）作为衡量指标。
回顾性收集了参与NP001两项2期安慰剂对照临床试验（ClinicalTrials.gov：NCT01281631和NCT02794857）的273例患者中的268例的盲态生存数据，这些患者根据实际体重接受了至少一剂1mg/kg或2mg/kg基于亚氯酸盐的NP001或安慰剂。采用Kaplan-Meier方法对意向性治疗人群估计生存概率。
在总体人群中，中位总生存期为4.8个月（2mg/kg NP001组为2.7年[95%CI：2.3，3.5]，安慰剂组为2.3年[95%CI：1.8，2.9]）。风险比（HR）：0.77（95%CI：0.57，1.03），P = 0.073。在年龄≤65岁的患者中，2mg/kg NP001组的中位总生存期为10.8个月（2mg/kg NP001组为3.3年[95%CI：2.4，3.8]，安慰剂组为2.4年[95%CI：1.7，3.3]）。HR：0.69（95%CI：0.50，0.95）。在1mg/kg NP001组或年龄>65岁的患者中未观察到差异。
本研究结果表明，NP001为期6个月的治疗疗程使肌萎缩侧索硬化症患者的总生存期增加了4.8个月。本研究结果表明，针对与先天性免疫系统相关的炎症可能为肌萎缩侧索硬化症的治疗提供新的治疗选择途径。
