“一石三鸟”阿尔茨海默病药物获批临床试验

与以往的单靶标疗法不同，Anavex 2-73是一种“一石三鸟”的新型疗法，旨在阻击与AD病理学相关的3个靶标：淀粉样蛋白、tau蛋白、炎症。...

Anavex是总部位于美国纽约的一家临床阶段的生物制药公司，专注于开发差异化的疗法用于神经退行性疾病和神经发育疾病的治疗，包括阿尔茨海默病（AD）、Rett综合征以及其他中枢神经系统疾病。



近日，该公司宣布，将在8月份启动一项IIb/III期临床试验，评估新型药物Anavex 2-73治疗早期AD的疗效和安全性。该研究是一项双盲、随机、安慰剂对照、48周研究，计划入组450例患者，这些患者将以1:1:1的比例随机接受2种剂量Anavex2-73或安慰剂的治疗。

与以往的单靶标疗法不同，Anavex 2-73是一种“一石三鸟”的新型疗法，旨在阻击与AD病理学相关的3个靶标：淀粉样蛋白、tau蛋白、炎症。之前，以淀粉样蛋白为靶标的数十个药物在临床研究中均已遭遇失败。

Anavex 2-73是一种sigma-1受体（S1R）跨膜蛋白激活剂，S1R作为一种分子伴侣和功能调节剂，被认为参与调节细胞内的稳态，通过减少诸如氧化应激、蛋白质错误折叠、线粒体功能障碍、炎症，来保持细胞处于健康、稳定的状态，所有这些在AD患者大脑中均存在。S1R激活已经证明能够减少AD的主要病理生理学标志：β淀粉样蛋白、过度磷酸化tau蛋白和炎症增加。

此前，在入组了32例澳大利亚早期AD患者的一项IIa期临床研究中，Anavex 2-73展现出了改善注意力水平、工作记忆以及改善精神运动功能的初步疗效。有些患者甚至恢复了已失去的机能，比如弹奏钢琴的能力。



Anavex公司总裁兼CEO Christopher U Missling博士表示，非常高兴能获得监管批准启动这项IIb/III期临床研究。该公司将利用IIa期研究中所发现的基因组生物标志物来筛选纳入IIb/III期研究的患者。

Anavex 2-73成功的希望或比较渺茫。特别是考虑到之前已经有数十种靶向淀粉样蛋白的药物、多种抗炎疗法（包括布洛芬）遭遇失败，而到目前为止，tau蛋白靶向疗法的结果也差强人意。不过，Anavex公司却认为，Anavex 2-73的广泛作用结合基因组学精准医学生物标志物驱动的临床研究设计，将有望提高该药的成功机会。







目前，Anavex公司也正在计划启动一项II期临床，评估Anavex 2-73治疗帕金森的潜力。除了Anavex 2-73之外，该公司临床前资产中还有几个治疗AD的药物，包括Anavex 3-71和Anavex 1-41。该公司神经管线资产如上图所示。Source:

Anavex Life Sciences Receives Approval To Initiate Phase 2b/3 Clinical Trial of ANAVEX®2-73 for the Treatment of Early Alzheimer’s Disease

• ANAVEX®2-73 Being Studied as Potential First Precision Medicine Biomarker-guided, Targeted Therapeutic in Alzheimer’s Disease
• Primary and Secondary Endpoints measuring Safety, and Cognitive and Functional Efficacy (ADAS-Cog, ADCS-ADL and CDR-SB)

NEW YORK – July 3, 2018 – Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental diseases including Alzheimer’s disease, Rett syndrome and other central nervous system (CNS) diseases, today announced that the Company has received approval by the Australian Human Research Ethics Committee to initiate its Phase 2b/3 double-blind, randomized, placebo-controlled, 48-week safety and efficacy trial of ANAVEX®2-73 for the treatment of early Alzheimer’s disease. The Phase 2b/3 study is scheduled to initiate enrollment of approximately 450 patients, randomized 1:1:1 to two different ANAVEX®2-73 doses or placebo within the next month. As part of the planned international study, North American sites will be added.

“We are extremely pleased to gain approval to initiate the ANAVEX®2-73 Phase 2b/3 study for the treatment of early Alzheimer’s disease, an area of very high unmet need for the growing number of patients around the world,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex.

The ANAVEX®2-73 Phase 2b/3 study design includes genomic precision medicine biomarkers identified in the ANAVEX®2-73 Phase 2a study. Primary and secondary endpoints will assess safety and both cognitive and functional efficacy, measured through ADAS-Cog, ADCS-ADL and CDR-SB. ANAVEX®2-73 Phase 2a Alzheimer’s disease study previously demonstrated dose dependent improvement in exploratory endpoints of cognition (MMSE) and function (ADCS-ADL).

About ANAVEX®2-73

ANAVEX®2-73 activates the Sigma-1 receptor (S1R) protein, which serves as a molecular chaperone and functional modulator involved in restoring homeostasis. S1R activation has demonstrated ability to reduce key pathophysiological signs of Alzheimer’s disease: beta amyloid, hyperphosphorylated tau, and increased inflammation. In a Phase 2a Alzheimer’s disease study, ANAVEX®2-73 has shown dose dependent improvement in exploratory endpoints of cognition (MMSE) and function (ADCS-ADL). Full genomic analysis of ANAVEX®2-73 Phase 2a Alzheimer’s disease patients was performed. The ANAVEX®2-73 Phase 2b/3 study design includes genomic precision medicine biomarkers identified in the ANAVEX®2-73 Phase 2a study.

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