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.
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This post is Copyright: | October 27, 2026
Neuro-Dementia