MedPath

FDA Grants Breakthrough Therapy Designation to Latozinemab for FTD-GRN

• The FDA has granted Breakthrough Therapy Designation to latozinemab for frontotemporal dementia with a progranulin gene mutation (FTD-GRN). • Latozinemab, developed by Alector and GSK, is a monoclonal antibody that elevates progranulin levels by blocking sortilin. • The designation was based on Phase 2 clinical trial data, indicating substantial improvement over available therapies for this rare, rapidly progressing disease. • Latozinemab is currently in a pivotal Phase 3 study (INFRONT-3), with target enrollment achieved in October 2023.

The FDA has granted Breakthrough Therapy Designation to latozinemab, an investigational human monoclonal antibody, for the treatment of frontotemporal dementia with a progranulin gene mutation (FTD-GRN). This designation aims to expedite the development and review of drugs that show promise in treating serious conditions where preliminary clinical evidence indicates substantial improvement over existing therapies.

Mechanism of Action and Clinical Development

Latozinemab, also known as AL001, is designed to elevate progranulin (PGRN) levels by inhibiting sortilin, a degradation receptor for PGRN. PGRN is a key regulator of immune activity in the brain, with genetic links to neurodegenerative disorders, including FTD, Alzheimer’s disease, and Parkinson’s disease. The drug is currently in the pivotal INFRONT-3 Phase 3 study, which completed target enrollment in October 2023.

Rationale for Breakthrough Therapy Designation

The FDA's decision was based on data from the INVOKE-2 Phase 2 clinical trial, which demonstrated latozinemab's potential to significantly improve outcomes for FTD-GRN patients. Breakthrough Therapy Designation is reserved for drugs that may offer a substantial improvement over available therapies for serious conditions.

Frontotemporal Dementia and Unmet Needs

FTD is a rare neurodegenerative disease and a common cause of early-onset dementia, affecting an estimated 50,000 to 60,000 people in the United States and roughly 110,000 in the European Union. FTD-GRN, a heritable form of FTD, accounts for 5% to 10% of all FTD cases. Patients typically develop symptoms such as behavioral changes, impaired judgment, and language difficulties in their 40s and 50s, with the disease progressing over 7-10 years. Currently, there are no FDA-approved treatments for any form of FTD.

Collaboration between Alector and GSK

Alector and GSK are collaborating on the global development and commercialization of progranulin-elevating monoclonal antibodies, including latozinemab. Under the terms of their agreement, Alector received $700 million in upfront payments and is eligible for up to $1.5 billion in additional milestone payments. In the United States, the companies will equally share profits and losses, while Alector will receive tiered royalties for sales outside the United States.

Quote from Alector's CEO

"In partnership with GSK, we are encouraged and excited by this FDA Breakthrough Designation," said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. "With this designation, we look forward to continued productive conversations with the FDA, recognizing the unmet need for people living with FTD-GRN, a serious condition for which there are no FDA-approved treatment options available."
Subscribe Icon

Stay Updated with Our Daily Newsletter

Get the latest pharmaceutical insights, research highlights, and industry updates delivered to your inbox every day.

Related Topics

Denali Therapeutics' Tividenofusp Alfa Receives FDA Breakthrough Therapy Designation for Hunter Syndrome

Denali Therapeutics' tividenofusp alfa (DNL310) has received Breakthrough Therapy Designation from the FDA for Hunter syndrome (MPS II).
The designation aims to expedite the development and review of tividenofusp alfa, a potential improvement over existing therapies.

FDA Grants Priority Review to Vatiquinone for Friedreich's Ataxia Treatment

The FDA has accepted PTC Therapeutics' NDA for vatiquinone, a potential treatment for Friedreich's ataxia (FA), granting it priority review.
Vatiquinone aims to address the unmet need for FA patients, particularly children, by targeting energetic and oxidative stress pathways.

FDA Grants Orphan Drug Designation to EXG110 Gene Therapy for Fabry Disease

The FDA has granted orphan drug designation to EXG110, a novel gene therapy developed by Exegenesis Bio for Fabry disease.
EXG110 is designed as a one-time treatment to deliver a genetic payload directly to liver and heart cells, potentially improving efficacy and safety.

FDA Approves PTC Therapeutics' Kebilidi, First Gene Therapy Dosed Directly into the Brain

The FDA has approved Kebilidi (eladocagene exuparvovec), a gene therapy by PTC Therapeutics, for aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic disorder.
Kebilidi is the first gene therapy approved in the U.S. that involves direct administration into the brain, offering a novel approach to treating AADC deficiency.

FDA Approves PTC Therapeutics' Kebilidi, First Direct-to-Brain Gene Therapy

The FDA has approved PTC Therapeutics' Kebilidi (eladocagene exuparvovec-tneq) for aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic disorder.
Kebilidi is the first gene therapy approved by the FDA that is administered directly into the brain, specifically targeting the putamen region.

Nipocalimab Receives FDA Breakthrough Therapy Designation for Sjögren's Disease

The FDA granted Breakthrough Therapy Designation to Johnson & Johnson's nipocalimab for moderate-to-severe Sjögren's disease, highlighting its potential to address unmet needs.
Nipocalimab is the first investigational FcRn blocker to show positive Phase 2 results in Sjögren's disease, marking a significant advancement in targeted therapy.

Nipocalimab Receives FDA Breakthrough Therapy Designation for Sjögren's Disease

Nipocalimab, a novel treatment developed by Johnson & Johnson, has been granted Breakthrough Therapy Designation by the FDA.
The designation targets the treatment of moderate-to-severe Sjögren's disease in adults, addressing a significant unmet medical need.

FDA Authorizes Phase 2a Trial of Progerinin for Hutchinson-Gilford Progeria Syndrome

The FDA has authorized a Phase 2a clinical trial for Progerinin, a novel drug developed by PRG Science & Technology for Progeria treatment.
The trial will evaluate Progerinin in combination with Zokinvy, the current standard of care, in 10 patients with Progeria and Progeroid Laminopathies.

FDA Clears Investigational New Drug Application for Adaptin Bio's Glioblastoma Therapy APTN-101

The FDA has cleared Adaptin Bio's investigational new drug application for APTN-101, a novel therapy for glioblastoma, a grade 4 malignant glioma.
APTN-101 utilizes Adaptin Bio's BRiTE platform to target EGFRvIII, a protein associated with aggressive brain tumors, and enhance T-cell delivery to the brain.

Sunvozertinib Granted FDA Breakthrough Therapy Designation for First-Line EGFR Exon 20 Insertion-Positive NSCLC

The FDA has granted Breakthrough Therapy Designation to sunvozertinib for first-line treatment of advanced NSCLC with EGFR exon 20 insertion mutations.
The designation is based on Phase I/II WU-KONG1 trial results, which showed a 78.6% objective response rate and 12.4 months median progression-free survival.

Reference News

[1]
FDA Grants Latozinemab Breakthrough Therapy Designation for Frontotemporal Dementia Due to a Progranulin Gene Mutation (FTD-GRN)
finance.yahoo.com · Feb 7, 2024

Latozinemab, developed by Alector, Inc. and GSK, received FDA Breakthrough Therapy Designation for treating FTD-GRN, a r...

© Copyright 2025. All Rights Reserved by MedPath
HomeTerms & ConditionsPrivacy Policy