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Peer-reviewedCC BY-NC 4.0Alzheimer's & Dementia

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

  • Adam Simmons1
  • Bradley Boeve2
  • Isabelle Le Ber3
  • Barbara Borroni4,5
  • Catherine Mummery6
  • Jonathan D. Rohrer7
  • Giovanna Zamboni8
  • Oezguer A. Onur9
  • James B. Rowe10
  • Adam L. Boxer11
  • Tina Schwabe12
  • Olga I. Kahn1
19 more authors
  • Julie Y. Huang13
  • Hua Long1
  • Ruchi Gupta1
  • Jinglin Zhong1
  • Caiyan Li1
  • Leonard Guizzetti14
  • Lawrence P. Carter15
  • Tuan Nguyen1
  • Tiffany W. Chow1
  • Balasubrahmanyam Budda1
  • Lovingly Park16
  • Sam Jackson17
  • Robert Paul1
  • Michael Ward1
  • Gary Romano1
  • Sara Kenkare‐Mitra1
  • Arnon Rosenthal1
  • Giacomo Salvadore1
  • Arthur J. Mayorga1
17 affiliations
  1. 1Alector, Inc. South San Francisco California USA
  2. 2Department of Neurology Mayo Clinic Rochester Minnesota USA
  3. 3Paris Brain Institute Pitié‐Salpêtrière Hospital Paris France
  4. 4Department of Clinical and Experimental Sciences University of Brescia Brescia Italy
  5. 5IRCCS Centro San Giovanni di Dio Fatebenefratelli Molecular Markers Laboratory Brescia Italy
  6. 6Dementia Research Centre, National Hospital for Neurology and Neurosurgery University College London Hospital London UK
  7. 7Dementia Research Centre, Queen Square Institute of Neurology University College London London UK
  8. 8Department of Biomedical Metabolic and Neural Sciences at the University of Modena and Reggio Emilia Modena Italy
  9. 9Department of Neurology, Faculty of Medicine and University Hospital Cologne University of Cologne Cologne Germany
  10. 10Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge Cambridge UK
  11. 11Weill Institute for Neurosciences University of California San Francisco San Francisco California USA
  12. 12Mariner Bio Consulting LLC Mill Valley California USA
  13. 13Neurocrine Biosciences San Diego California USA
  14. 14Everest Clinical Research Markham Ontario Canada
  15. 15Mirum Pharmaceuticals Foster City California USA
  16. 16Eli Lilly Indianapolis Indiana USA
  17. 17Aditum Bio Oakland California USA
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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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Cite

BibTeXRIS
BibTeX
@article{simmons2026phase,
  title = {{Phase 3 randomized trial of latozinemab in frontotemporal dementia due to GRN mutations}},
  author = {Adam Simmons and Bradley Boeve and Isabelle Le Ber and Barbara Borroni and Catherine Mummery and Jonathan D. Rohrer and Giovanna Zamboni and Oezguer A. Onur and James B. Rowe and Adam L. Boxer and Tina Schwabe and Olga I. Kahn and Julie Y. Huang and Hua Long and Ruchi Gupta and Jinglin Zhong and Caiyan Li and Leonard Guizzetti and Lawrence P. Carter and Tuan Nguyen and Tiffany W. Chow and Balasubrahmanyam Budda and Lovingly Park and Sam Jackson and Robert Paul and Michael Ward and Gary Romano and Sara Kenkare‐Mitra and Arnon Rosenthal and Giacomo Salvadore and Arthur J. Mayorga},
  journal = {Alzheimer's \& Dementia},
  year = {2026},
  month = oct,
  doi = {10.1002/alz.71947},
  url = {https://doi.org/10.1002/alz.71947},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Phase 3 randomized trial of latozinemab in frontotemporal dementia due to GRN mutations
AU  - Adam Simmons
AU  - Bradley Boeve
AU  - Isabelle Le Ber
AU  - Barbara Borroni
AU  - Catherine Mummery
AU  - Jonathan D. Rohrer
AU  - Giovanna Zamboni
AU  - Oezguer A. Onur
AU  - James B. Rowe
AU  - Adam L. Boxer
AU  - Tina Schwabe
AU  - Olga I. Kahn
AU  - Julie Y. Huang
AU  - Hua Long
AU  - Ruchi Gupta
AU  - Jinglin Zhong
AU  - Caiyan Li
AU  - Leonard Guizzetti
AU  - Lawrence P. Carter
AU  - Tuan Nguyen
AU  - Tiffany W. Chow
AU  - Balasubrahmanyam Budda
AU  - Lovingly Park
AU  - Sam Jackson
AU  - Robert Paul
AU  - Michael Ward
AU  - Gary Romano
AU  - Sara Kenkare‐Mitra
AU  - Arnon Rosenthal
AU  - Giacomo Salvadore
AU  - Arthur J. Mayorga
PY  - 2026
DA  - 2026/10/26
JO  - Alzheimer's & Dementia
DO  - 10.1002/alz.71947
UR  - https://doi.org/10.1002/alz.71947
AB  - 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.
SN  - 1552-5260
SN  - 1552-5279
ER  -