Alector's Alzheimer’s Initiative with AbbVie Falls Short in Phase II Trials, Resulting in a 17% Workforce Reduction

Alector’s Alzheimer’s Initiative with AbbVie Falls Short in Phase II Trials, Resulting in a 17% Workforce Reduction

Alector's Alzheimer’s Initiative with AbbVie Falls Short in Phase II Trials, Resulting in a 17% Workforce Reduction

On Monday, Alector declared that its investigational antibody, AL002, did not succeed in the Phase II INVOKE-2 trial, failing to demonstrate a significant reduction in clinical progression for Alzheimer’s patients.

The press release provided limited details, merely stating that AL002 “did not achieve the primary efficacy endpoint,” assessed through the Clinical Dementia Rating Sum of Boxes tool. Furthermore, the drug did not show significant effects on essential secondary and functional outcomes, nor did it demonstrate notable improvements in liquid and imaging biomarkers, including brain amyloid levels.

In terms of safety, the INVOKE-2 study reported occurrences of amyloid-related imaging abnormalities (ARIA) and infusion-related reactions among patients treated with AL002.

Following the announcement, Alector’s stock plummeted by 31% during after-hours trading on Monday, according to a report from Seeking Alpha.

In a note to their investors, analysts at Stifel Partners characterized the results of the INVOKE-2 trial as an “outright failure” and a “major setback” for Alector. They expressed that they believed the AL002 trial in [Alzheimer’s disease] had a genuine opportunity for success due to strong genetic and biomarker support for the target, also noting the roughly 20% rate of ARIA associated with the drug, which suggested impact on amyloid.

“Although the [press release] provides few details, it appears that the trial was a conclusive failure,” the Stifel note indicated. Alector is now nearly entirely reliant on its candidate for frontotemporal dementia, AL001, and its “blood-brain-barrier platform, which remains largely untested.”

Given these unsatisfactory mid-stage results, Alector will terminate its long-term extension study for AL002. On the same day, the biotech announced a resource realignment strategy that will involve approximately 41 layoffs, equating to about 17% of its current workforce, as detailed in an SEC filing.

The layoffs are expected to take effect in the first half of 2025, during which Alector anticipates incurring .9 million in one-time restructuring expenses, primarily for severance, salaries, and other personnel costs. As of September 30, 2024, Alector had roughly 7 million in cash, cash equivalents, and investments, sufficient to sustain operations until 2026, the company reported.

AL002 is a humanized monoclonal antibody investigation designed to enhance the function of the TREM2 protein, a crucial membrane receptor on microglial cells that aid in maintaining neuronal networks and repairing brain tissue injuries.

Patients suffering from Alzheimer’s disease commonly display various TREM2 mutations and impeded receptor functionality, both of which are linked to a heightened disease risk. In contrast, increased TREM2 concentrations in cerebrospinal fluid have been associated with reduced amyloid and tau accumulation in the brain, contributing to a generally slower cognitive decline.

In October 2017, AbbVie recognized the potential of AL002’s mechanism, investing 5 million upfront for global rights to develop and commercialize it alongside another Alzheimer’s disease candidate. However, in July 2022, AbbVie opted to discontinue its work on AL003 while retaining AL002. According to Alector’s pipeline page, the company has also ceased all efforts related to AL003.