Key Takeaways:
- Alector is discontinuing the development of latozinemab for frontotemporal dementia (FTD) after it failed to meet its primary endpoint in the INFRONT-3 Phase 3 trial.
- The company will reduce its workforce by nearly half, and its president and R&D head will depart.
- Despite the setback, Alector’s partnership with GSK remains active, with a focus now shifting to an ongoing Phase 2 trial for an Alzheimer’s antibody.
Alector Therapeutics has announced it will discontinue development of its investigational antibody latozinemab following a phase 3 failure in frontotemporal dementia (FTD). The company will also reduce its workforce by nearly half and see the departure of its president and head of R&D, Sara Kenkare-Mitra, Ph.D., effective December 22, according to an October 22 press release.
INFRONT-3 Trial Fails to Show Clinical Benefit
The decision follows results from the INFRONT-3 phase 3 trial, which tested latozinemab in patients with FTD caused by mutations in the progranulin (PGRN) gene. While the antibody successfully reduced plasma PGRN concentrations, it failed to slow disease progression as assessed by industry-standard scales. Alector reported that latozinemab also showed no effect on disease measures based on fluid biomarkers or volumetric magnetic resonance imaging.
“While latozinemab did not demonstrate a clinical benefit in INFRONT-3, the insights gained are invaluable for understanding progranulin-related neurodegeneration,” said Alector’s Chief Medical Officer Giacomo Salvadore, M.D. The company expressed gratitude toward the patients, caregivers, and investigators involved in the study.
As a result of the outcome, Alector is discontinuing both the open-label extension of INFRONT-3 and a continuation study of latozinemab. The antibody, designed to raise progranulin levels by blocking the protein sortilin, was intended to address the loss of progranulin linked to certain forms of FTD.
Market Reaction and Future Focus
Analysts from William Blair described the trial’s outcome as disappointing, noting that restoring progranulin did not translate to clinical benefit in this patient population. They also observed a significant market reaction, with Alector’s stock price dropping about 50% after the announcement, from $3.21 to $1.56 per share on October 22.
The company said it will now prioritize its ongoing phase 2 Alzheimer’s trial under the same partnership with GSK. The study, called PROGRESS-AD, is evaluating nivisnebart—another sortilin-targeting antibody—in 367 patients with early-stage Alzheimer’s disease. Enrollment was completed in April, with full trial completion expected next year and interim data analysis planned for the first half of 2026.
GSK entered its collaboration with Alector in 2021 through a deal valued at up to $2.2 billion, including $700 million upfront to co-develop latozinemab and another antibody, AL101. Alector confirmed that its partnership with GSK remains active despite the discontinuation of latozinemab.
Broader Pipeline and Previous Setbacks
Alongside its partnered programs, Alector continues to advance several preclinical, wholly owned assets. These include AL137, an anti-amyloid beta antibody for Alzheimer’s disease; AL050, an enzyme replacement therapy for Parkinson’s disease; and an siRNA platform.
The restructuring marks the company’s second major pipeline setback in a year. In late 2024, Alector halted development of its AbbVie-partnered Alzheimer’s antibody AL002 after it failed in a phase 2 study, leading to a 17% workforce reduction.
Alector stated that it is analyzing data from the INFRONT-3 trial and plans to present detailed findings at an upcoming medical meeting.
In addition, for the FTD research field, the trial data from INFRONT-3 may still yield valuable scientific learnings—such as the relationship between progranulin restoration and clinical outcomes, or potential subgroup analyses in FTD-GRN populations. AFTD
Expanded considerations and reflections
While the decision is undoubtedly a setback, it also provides an opportunity for the FTD research community to reflect on next steps. For instance:
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Could earlier intervention in FTD (before significant neurodegeneration) or via prevention settings yield different results?
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Are alternate mechanisms beyond progranulin elevation required to truly impact the course of FTD?
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How can future trials in FTD better incorporate imaging, functional endpoints, and real-world data to capture meaningful change?
For patients, families and clinicians working in FTD, the news serves as a reminder of the complexity of brain diseases and the need for caution but also perseverance. Each trial—even when negative—adds to the collective knowledge and may guide the design of future studies.
