Registry Closes the File on a Genetic FTD Trial Whose Result Was Already Known

ClinicalTrials.gov now lists Alector and GSK's Phase 3 INFRONT-3 trial of the anti-sortilin antibody latozinemab as "Completed," a formal registry update dated January 6, 2026 that follows the sponsor's October 2025 disclosure that the drug raised a target biomarker but did not slow disease in people with FTD caused by a progranulin gene mutation.

The public trial record for INFRONT-3 (NCT04374136), the Phase 3 study of latozinemab (also called AL001) in frontotemporal dementia due to a progranulin gene mutation (FTD-GRN), now shows an overall status of "Completed," with the registry update posted January 6, 2026. The change is administrative, but it closes out one of the few late-stage disease-modifying trials in genetic FTD, and it arrives months after the substantive news: on October 21, 2025, Alector, developing the antibody with GSK, reported that the 96-week, double-blind, placebo-controlled trial had not met its clinical co-primary endpoint.

INFRONT-3 enrolled 119 people with a heterozygous GRN mutation, including a primary analysis population of roughly 102 symptomatic adults with behavioral variant FTD or primary progressive aphasia, according to a trial abstract presented at the American Academy of Neurology's 2026 annual meeting. Participants received monthly infusions of latozinemab, an antibody designed to block the sortilin receptor and raise blood and brain levels of progranulin, a protein that is deficient in people who carry a GRN mutation. The trial did what it was designed to do at the molecular level: plasma progranulin rose 165 percent compared with placebo at week 96 (p less than 0.0001), meeting the biomarker co-primary endpoint and confirming the antibody engaged its target. But on the clinical co-primary endpoint, a combined dementia rating and functional scale (CDR plus NACC FTLD Sum of Boxes), there was no evidence latozinemab slowed decline relative to placebo. Secondary and exploratory measures, including fluid biomarkers of nerve damage and brain volume on MRI, also showed no treatment-related effect. Following the result, Alector discontinued the trial's open-label extension and canceled a planned continuation study.

The outcome extends a difficult year for Alector's antibody pipeline in neurodegeneration. This newspaper previously reported that the company's anti-TREM2 antibody, AL002, failed a completed Phase 2 trial in Alzheimer's disease, with its extension study halted. With INFRONT-3 now also closed out negative on its clinical goal, both of the company's principal late-stage antibody programs against neurodegenerative disease have ended without demonstrating a clinical benefit, narrowing an already thin field of disease-modifying candidates for genetic FTD.

Researchers and patient advocacy groups have noted a counterpoint: the biomarker result shows that raising progranulin levels in the blood is achievable and was not accompanied by new safety concerns, so the underlying strategy of correcting progranulin deficiency has not been ruled out. Other programs aimed at the same GRN pathway through different approaches, including an AAV gene therapy and an oral small molecule, remain in earlier-phase testing, according to a genetic FTD trials update from the AFTD patient organization.

Alector has said the full INFRONT-3 dataset would be presented at a medical meeting; no further trials of latozinemab in FTD-GRN are currently planned by the company.