Phase 3 randomized trial of latozinemab in frontotemporal dementia due to GRN mutations

Why clinicians should know about it

• Picked for Neurology (clinical) (top studies of the week, 8 November 2026): Phase III trial tests disease-modifying therapy for genetic FTD

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.

Abstract as published, via PubMed.