Alector, Inc. announced that it has completed enrollment in INVOKE-2, the Phase 2 clinical trial of AL002. INVOKE-2 is evaluating the safety and efficacy of AL002 in slowing disease progression in individuals with early Alzheimer?s disease (AD). Data from the trial are expected in the fourth quarter of 2024.

AL002 is a novel investigational humanized monoclonal antibody (mAb) that binds to triggering receptor expressed on myeloid cells 2 (TREM2). AL002 is the most advanced TREM2 activating product candidate in clinical trials and is being developed in collaboration with AbbVie. INVOKE-2 is a randomized, double-blind, placebo-controlled, dose-ranging, multi-center Phase 2 clinical trial being conducted at multiple sites across 11 countries.

Participants with early AD are randomized to receive AL002 or placebo administered intravenously every four weeks. The trial utilizes a common close design with up to 96 weeks of randomized treatment, and all participants remain on their assigned regimen until the last participant completes 48 weeks of treatment. This design provides the opportunity to capture more observations for the primary analysis.

The primary endpoint is disease progression as measured by the Clinical Dementia Rating Sum of Boxes (CDR®-SB). The CDR-SB, which is used to assess (score) the severity of AD, is a validated instrument that assesses both cognitive and functional domains and is the accepted efficacy endpoint for FDA. The trial also employs other multiple clinical and functional outcome assessments.

Additionally, the trial includes cerebrospinal fluid (CSF) and plasma biomarkers assessing microglial activation and Alzheimer?s pathophysiology, as well as brain magnetic resonance imaging (MRI) and amyloid beta and tau positron emission tomography (PET) imaging. At the 2023 Alzheimer?s Association International Conference (AAIC) in July, Alector presented an update on INVOKE-2. The presentation highlighted previously reported treatment-emergent MRI findings observed in INVOKE-2 that resemble amyloid-related imaging abnormalities (ARIA). It is unknown whether the biological mechanism(s) causing these MRI changes are the same as that associated with the ARIA that has been described with anti-amyloid beta antibodies.

It is hypothesized that AL002 may provide potential benefit alone or in combination with anti-amyloid beta antibodies by potentially harnessing the broader beneficial effects of microglia. Microglia activation may not only enhance the clearance of misfolded proteins that accumulate and form amyloid plaques but may also perform other supportive microglia functions, including maintenance of neuronal and synaptic health, and warrants further investigation.