Alector has revealed that in a Phase III clinical trial in individuals with frontotemporal dementia due to a progranulin gene mutation (FTD-GRN) its candidate latozinemab (AL001) did not meet the clinical co-primary endpoint. 

Based on the results, the company has announced that the open-label extension portion of the INFRONT-3 trial and the continuation study for latozinemab will be discontinued. 

Alector is also reducing its workforce by approximately 49% to focus resources on its highest-priority programmes. Shares of the company fell over 55% following the announcement. 

Latozinemab failed to slow FTD-GRN progression, as measured by the Clinical Dementia Rating (CDR) plus National Alzheimer’s Coordinating Center Frontotemporal Lobar Degeneration Sum of Boxes (CDR plus NACC FTLD-SB).  

Although treatment resulted in a statistically significant effect on the biomarker co-primary endpoint of plasma progranulin (PGRN) concentrations, the secondary and exploratory endpoints, such as fluid biomarkers and volumetric magnetic resonance imaging (vMRI), demonstrated no treatment-related effects on FTD-GRN. 

“While latozinemab did not demonstrate a clinical benefit in INFRONT-3, the insights gained are invaluable for understanding progranulin-related neurodegeneration,” said Giacomo Salvadore, Chief Medical Officer of Alector. “We extend our deepest gratitude to the patients, caregivers, and investigators who made this trial possible, and we plan to share the results with the scientific community to support continued progress in understanding progranulin biology and FTD pathophysiology.” 

Alector will continue its collaboration with GSK on nivisnebart (AL101/GSK4527226), which is being evaluated in the Phase II PROGRESS-AD trial in early Alzheimer’s disease (AD). 

The company is also progressing multiple preclinical programmes using its Alector Brain Carrier (ABC) technology. These include AL137 for its ABC-enabled anti-amyloid beta (Aβ) antibody programme in AD, AL050 for its ABC-enabled glucocerebrosidase (GCase) enzyme replacement therapy programme in Parkinson’s, and ADP064-ABC for its siRNA programme targeting tau for AD and FTD.

Diana Turner, Deputy Editor, DDW