Alector's investigational antibody AL002, partnered with AbbVie, has failed to demonstrate efficacy in the Phase II INVOKE-2 study for Alzheimer's disease, leading to a significant setback for the company and triggering a 17% workforce reduction. The trial did not meet its primary endpoint, measured by the Clinical Dementia Rating Sum of Boxes tool, and showed no treatment effects on key secondary, functional, or imaging biomarkers, including brain amyloid levels.
Lack of Efficacy and Safety Signals
According to Alector's press release, AL002 did not significantly slow clinical progression in patients with Alzheimer's disease. Furthermore, the study revealed evidence of amyloid-related imaging abnormalities (ARIA) and infusion-related reactions in patients treated with AL002, raising safety concerns. Stifel Partners analysts described the INVOKE-2 readout as an "outright failure," noting that the results were a "significant setback" for Alector, despite promising genetic and biomarker evidence for the target.
Company Response and Future Plans
In response to the trial's failure, Alector is discontinuing its long-term extension study for AL002 and implementing a resource realignment initiative. This initiative will involve laying off approximately 41 employees, representing 17% of the company's current workforce. The layoffs are expected to be implemented in the first half of 2025, incurring one-time restructuring costs of approximately $3.9 million, primarily related to severance payments and personnel expenses. Despite the setback, Alector maintains that its existing cash reserves of $457 million as of September 30, 2024, will be sufficient to fund operations through 2026.
AL002 Mechanism of Action
AL002 is a humanized monoclonal antibody designed to enhance the function of TREM2, a key membrane receptor in microglia cells. Microglia play a crucial role in maintaining neuronal networks and repairing tissue injuries in the brain. Patients with Alzheimer's disease often exhibit TREM2 mutations and impaired receptor function, which are associated with an increased risk of the disease. Conversely, higher concentrations of TREM2 in cerebrospinal fluid have been correlated with lower amyloid and tau buildup in the brain and slower cognitive decline.
Collaboration History and Market Impact
AbbVie initially invested in AL002's mechanism of action in October 2017, paying $205 million upfront for the global option to develop and commercialize it along with another Alzheimer's disease candidate. However, in July 2022, AbbVie dropped AL003 but retained AL002. Following the announcement of the Phase II failure, Alector's stock price plummeted by 31% in after-hours trading, reflecting investor disappointment and uncertainty about the company's future prospects.
