Phase 3 randomized trial of latozinemab in frontotemporal dementia due to GRN mutations
Abstract
Abstract INTRODUCTION Heterozygous progranulin gene mutations causing frontotemporal dementia (FTD‐GRN) are associated with deficiency in progranulin (PGRN). Latozinemab is a human monoclonal immunoglobulin G1 (IgG1) antibody designed to elevate PGRN levels in people with heterozygous loss‐of‐function (LOF) GRN mutations.
Methods
A pivotal phase 3 trial, INFRONT‐3 (NCT04374136), evaluated the efficacy, safety, and biomarker changes of 60 mg/kg of intravenously administered latozinemab or placebo every 4 weeks for 96 weeks in participants who have or are at risk for FTD due to heterozygous LOF GRN mutations. Those completing the double‐blind phase could enter a 96‐week open‐label safety extension.
Results
Although latozinemab administration resulted in sustained elevation of plasma and CSF PGRN concentrations in symptomatic participants with FTD‐GRN (primary analysis population), there was no treatment‐related slowing of disease progression as measured by clinical or biomarker assessments. No adverse safety signals were identified.
Discussion
INFRONT‐3 provides the first phase 3 efficacy and safety results for an investigational therapy in FTD‐GRN.