On Monday, Alector, Inc. (NASDAQ:ALEC) released results from the INVOKE-2 Phase 2 trial evaluating the safety and efficacy of AL002 in slowing disease progression in individuals with early Alzheimer's disease (AD).
AL002 failed to meet the primary endpoint of slowing Alzheimer's clinical progression as measured by the Clinical Dementia Rating Sum of Boxes (CDR-SB).
Also, no treatment effects favored AL002 on secondary clinical and functional endpoints.
The company says treatment with AL002 resulted in sustained target engagement and pharmacodynamic responses indicative of microglial activation.
Similarly, there were no significant effects on Alzheimer's fluid biomarkers favoring AL002, and amyloid PET imaging demonstrated no treatment-related reduction of brain amyloid levels.
As previously reported, INVOKE-2 showed MRI changes resembling amyloid-related imaging abnormalities (ARIA) and infusion-related reactions. ARIA was primarily seen in participants treated with AL002.
Based on the results, Alector is stopping the long-term extension study.
Alector's focus are progranulin-elevating programs, latozinemab, and AL101/GSK4527226, developed in collaboration with GSK Plc (NYSE:GSK).
Topline data from the pivotal INFRONT-3 Phase 3 trial of latozinemab in frontotemporal dementia with a progranulin gene mutation is expected in late 2025 or early 2026.
PROGRESS-AD Phase 2 trial of AL101/GSK4527226 in early AD reached over one-third of its target enrollment of 282 participants. Alector is also advancing its preclinical candidates aimed at a broad and diverse range of protein and enzyme targets.
To align resources with these strategic priorities, Alector is reducing its workforce by approximately 17%.
As of September 30, 2024, Alector has $457.2 million in cash, cash equivalents, and investments, which the company continues to expect will provide a runway through 2026.
William Blair expressed surprise and disappointment at the update, given the strong scientific basis, evidence of target engagement, and potential signs of disease modification tied to ARIA cases. The analyst maintained the Outperform rating.
Despite still seeing promise in TREM2 as a target and in neuroinflammatory modulation, the firm is removing AL002 from its model due to the study's failure, underscoring the difficulties in developing treatments for neurodegenerative diseases.
The analyst also expects AbbVie Inc (NYSE:ABBV) to opt out of the program partnership and forgo the potential $250 million licensing payment.
AbbVie has an exclusive option to develop and commercialize AL002 globally.
Price Action: ALEC stock is down 37.3% at $2.485 at last check Tuesday.
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週一，Alector, Inc.（納斯達克股票代碼：ALEC）公佈了 INVOKE-2 二期試驗的結果，該試驗評估了 AL002 在減緩早期阿爾茨海默氏病（AD）患者疾病進展方面的安全性和有效性。
根據臨床癡呆評級方框總和（CDR-SB）測量，AL002 未能達到減緩阿爾茨海默氏症臨床進展的主要終點。
此外，在次要臨床和功能終點上，沒有任何治療效果有利於 AL002。
該公司表示，使用 AL002 進行治療可使靶標持續參與併產生藥效學反應，表明小膠質細胞激活。
同樣，對有利於 AL002 的阿爾茨海默氏症液體生物標誌物沒有顯著影響，澱粉樣蛋白 pET 成像顯示，與治療相關的腦澱粉樣蛋白水平沒有降低。
正如先前報道的那樣，INVOKE-2 顯示出類似於澱粉樣蛋白相關影像異常 (ARIA) 和輸液相關反應的磁共振成像變化。ARIA 主要出現在接受 AL002 治療的參與者身上。
根據結果，Alector正在停止長期延期研究。
Alector的重點是與葛蘭素集團（紐約證券交易所代碼：GSK）合作開發的progranulin提升程序、latozinemab和AL101/GSK4527226。
拉託津單抗治療具有progranulin基因突變的額瞼癡呆的關鍵Infront-3三期試驗的主要數據預計將於2025年底或2026年初公佈。
公元初期AL101/GSK4527226的PROGRESS-AD二期試驗已達到其282名參與者目標註冊人數的三分之一以上。Alector還在推進其針對廣泛多樣的蛋白質和酶靶標的臨床前候選藥物。
爲了使資源與這些戰略優先事項保持一致，Alector正在裁員約17％。
截至2024年9月30日，Alector擁有4.572億美元的現金、現金等價物和投資，該公司繼續預計，這些資金將在2026年之前提供一條跑道。
鑑於有力的科學依據、靶點參與的證據以及與ARIA病例相關的潛在疾病改變跡象，威廉·布萊爾對這一更新表示驚訝和失望。該分析師維持跑贏大盤的評級。
儘管仍將 TREM2 作爲靶標和神經炎症調節前景，但由於該研究的失敗，該公司正在將 AL002 從其模型中刪除，這凸顯了開發神經退行性疾病治療方法的困難。
該分析師還預計，艾伯維公司（紐約證券交易所代碼：ABBV）將選擇退出該計劃的合作伙伴關係，放棄可能的2.5億美元許可付款。
艾伯維擁有在全球開發和商業化 AL002 的獨家選擇。
價格走勢：週二最後一次檢查時，ALEC股價下跌37.3％，至2.485美元。
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