Alector, Inc. discontinues Phase 2 PROGRESS-AD trial of nivisnebart in early Alzheimer’s disease after futility analysis shows it is unlikely to meet the primary endpoint.
Written By: Pharmacally Medical News Desk
Alector, Inc. has discontinued its Phase 2 PROGRESS-AD trial evaluating nivisnebart (AL101/GSK4527226) in individuals with early Alzheimer’s disease after a pre-specified futility analysis by an independent data monitoring committee (IDMC) indicated that the study was unlikely to achieve its primary endpoint of slowing disease progression.
Nivisnebart is an investigational human monoclonal antibody designed to block and downregulate the sortilin receptor, thereby increasing levels of progranulin (PGRN) in the brain. Progranulin is a protein involved in lysosomal function, neuronal survival, and the regulation of inflammation, and has been genetically linked to several neurodegenerative disorders. The program is being co-developed with GSK.
Chief Executive Officer Arnon Rosenthal stated that the outcome is disappointing for patients and families affected by Alzheimer’s disease and underscores the complexity of developing effective treatments for neurodegeneration. He acknowledged the contributions of trial participants, caregivers, investigators, and study staff, and noted that the study has added to the scientific understanding of progranulin biology in Alzheimer’s disease.
The companies will coordinate with investigators to inform participants about the discontinuation, and detailed results from the study are expected to be presented at a future scientific meeting.
Alector stated that it remains focused on advancing its broader pipeline targeting neurodegenerative diseases through approaches aimed at removing toxic proteins, replacing deficient proteins, and restoring immune and neuronal function.
Central to this strategy is the company’s proprietary Alector Brain Carrier (ABC) platform, developed to enhance drug delivery across the blood–brain barrier and enable peripheral dosing across multiple therapeutic modalities.
The company continues to advance several ABC-enabled programs, including AL037/AL137, an anti-amyloid beta antibody in IND-enabling studies with a planned IND submission in the first quarter of 2027, and AL064/AL164, a tau-targeting siRNA candidate progressing toward early clinical development. Additional programs include candidates targeting alpha-synuclein and NLRP3, as well as AL050, an engineered glucocerebrosidase enzyme replacement therapy for Parkinson’s disease, with an IND filing planned for 2027.
Reference