Anavex Reports Phase III Results for Alzheimer's Drug Targeting SIGMAR1 Gene
Anavex Reports Phase III Results for Alzheimer's Drug Targeting SIGMAR1 Gene
This was confirmed in the Phase IIb/III study analysis: Over 48 weeks, blarcamesine significantly slowed clinical progression by 36.3% in the primary endpoint ADAS-Cog13 [LS mean ADAS-Cog13 difference of -2.027; Anavex Life Sciences Corp. ("Anavex" or the "Company") (NASDAQ:AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders including Alzheimer's disease, Parkinson's disease, Rett syndrome, schizophrenia, and other central nervous system (CNS) diseases, today presented new data from the Phase IIb/III study showing that blarcamesine (ANAVEX2-73), once daily orally, demonstrates pre-specified clinical efficacy through upstream SIGMAR1 activation.
安維生命科學公司（"Anavex"或"公司"）（NASDAQ:AVXL）是一家臨床階段的生物製藥公司，開發針對神經退行性、神經發育性和神經精神疾病，包括阿爾茨海默病、帕金森病、瑞特綜合徵、精神分裂症和其他中樞神經系統（CNS）疾病的差異化治療藥物。今天，公司發佈了來自IIb/III期研究的新數據，顯示一天一次口服的blarcamesine（ANAVEX2-73）通過上游SIGMAR1激活表現出預先確定的臨床療效。
Clinical data confirmed the mechanism of action (MoA) by pre-specified SIGMAR1 gene analysis in people with early Alzheimer's disease (AD). The data were presented by Marwan Noel Sabbagh, MD, Professor of Neurology at Barrow Neurological Institute and Chairman of the Anavex Scientific Advisory Board at the Clinical Trials on Alzheimer's Disease (CTAD) conference, which is taking place October 29 - November 1, 2024, in Madrid, Spain.
臨床數據證實了在早期阿爾茨海默病（AD）患者中通過預先確定的SIGMAR1基因分析來確定作用機制（MoA）。這些數據由巴羅神經科學研究所的神經學教授、安維生命科學科學顧問委員會主席Marwan Noel Sabbagh, MD在現正在西班牙馬德里舉行的阿爾茨海默病臨床試驗（CTAD）會議上展示。
SIGMAR1 is an integral membrane protein which activates an upstream compensatory process: Blarcamesine induces autophagy through SIGMAR1 activation resulting in restoring cellular homeostasis. In Alzheimer's disease patients, mutations (variants) of genes have generally been identified as disease risk factors. Likewise, impaired SIGMAR1 function (gene mutation, variants) leads to potential suboptimal function. Hence, patients who carry the non-mutated, common SIGMAR1 wild type (WT)1 gene, are expected to have stronger beneficial response to blarcamesine than patients with a SIGMAR1 mutation (variant), who nevertheless also benefited from treatment.2
SIGMAR1是一種整合膜蛋白，它通過上游的補償過程激活blarcamesine，通過SIGMAR1激活誘導自噬，從而恢復細胞內穩態。在阿爾茨海默病患者中，基因變異（變種）通常被鑑定爲疾病風險因素。同樣，受損的SIGMAR1功能（基因突變、變種）會導致潛在的亞優異功能。因此，攜帶非突變的常見SIGMAR1野生型（WT）基因的患者，預計對blarcamesine有更強的受益反應，而患有SIGMAR1突變（變種）的患者，儘管也從治療中受益。
This was confirmed in the Phase IIb/III study analysis: Over 48 weeks, blarcamesine significantly slowed clinical progression by 36.3% in the primary endpoint ADAS-Cog13 [LS mean ADAS-Cog13 difference of -2.027; P=0.008] in the ITT analysis. This signal was even stronger in the pre-specified common SIGMAR1 wild type (WT) group with slowed clinical progression by 49.8% at 48 weeks in the active group vs. placebo, respectively [LS mean ADAS-Cog13 difference of -2.317; P=0.015]. Equal analysis with CDR-SB led to comparable consistent results.
這在IIb/III期研究分析中得到證實：48周內，blarcamesine在ITt分析中明顯減緩了36.3%的臨床進展，ADAS-Cog13 [LS均ADAS-Cog13差異爲-2.027；P=0.008]。這一信號在預先確定的常見SIGMAR1野生型（WT）群體中更加強烈，在48周內，活性組與安慰劑組相比分別減緩了49.8%的臨床進展[LS均ADAS-Cog13差異爲-2.317；P=0.015]。使用CDR-Sb進行相等分析得出了可比一致的結果。
