Alector's Dementia Drug Failure Leads to Layoffs and Pipeline Shift
Alector Therapeutics, a California-based biotech company, has announced the discontinuation of its investigational antibody latozinemab following disappointing results from a late-stage clinical trial. The drug, which was being developed in partnership with GSK for the treatment of frontotemporal dementia (FTD), failed to meet its primary endpoint of slowing disease progression in patients with a specific genetic mutation.
Trial Results and Company Response
The Phase III INFRONT-3 trial, which enrolled 119 patients with FTD caused by progranulin gene mutations, showed that while latozinemab successfully reduced plasma progranulin concentrations, it did not translate to clinical benefits. The drug failed to demonstrate a significant effect on disease progression compared to placebo and missed key secondary endpoints, including volumetric magnetic resonance imaging outcomes and other fluid biomarker concentrations.
In response to these results, Alector has announced a significant restructuring:
- Discontinuation of the open-label extension of INFRONT-3 and a continuation study of latozinemab
- Layoffs affecting approximately 49% of its workforce, potentially impacting around 116 employees
- The resignation of Sara Kenkare-Mitra, Ph.D., Alector's president and head of R&D, effective December 22, 2025
Dr. Giacomo Salvadore, Alector's Chief Medical Officer, stated, "While latozinemab did not demonstrate a clinical benefit in INFRONT-3, the insights gained are invaluable for understanding progranulin-related neurodegeneration."
Financial Impact and Future Directions
The news of the trial failure and subsequent restructuring has had a significant impact on Alector's stock price, which plummeted by 51% to $1.56 per share in after-hours trading. Despite this setback, the company reports having $291.1 million in cash, cash equivalents, and short-term investments as of September 30, 2025, which it believes will fund operations through 2027.
Alector is now shifting its focus to other pipeline assets:
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Nivisnebart (AL101): Another GSK-partnered asset currently in the Phase II PROGRESS-AD trial for early Alzheimer's disease, with an interim analysis expected in the first half of 2026.
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Preclinical assets: Including AL137, an anti-amyloid beta antibody for Alzheimer's disease, and AL050, an enzyme replacement therapy for Parkinson's disease.
The company maintains its collaboration with GSK, which invested $700 million upfront in 2021 for the co-development of latozinemab and AL101, with potential milestone payments of up to $1.5 billion.
This setback represents Alector's second failed neurodegenerative asset in a year, following the discontinuation of an AbbVie-partnered Alzheimer's drug in late 2024, which also resulted in a 17% workforce reduction at that time.
References
- Alector Scraps Dementia Drug After Phase III Flop, Lays Off 49% of Staff
This represents Alector's second failed neurodegenerative asset in a year, after an AbbVie-partnered asset missed in Alzheimer's last November. On latozinemab for frontotemporal dementia, Alector was working with GSK, which fronted $700 million in 2021 to collaborate on two programs.
- Alector dementia drug, partnered with GSK, fails in key study
The negative readout led to a collapse in share price for Alector, which now plans to cut almost half of its workforce while refocusing and finding a new R&D leader.
- Alector halves staff after GSK-partnered antibody flops phase 3 dementia trial
Alector Therapeutics is shelving a GSK-partnered antibody after the asset failed to slow disease progression in patients with a variety of frontotemporal dementia (FTD). To pivot away from latozinemab, the Bay Area biotech is laying off 49% of its staff, while the company’s president and head of R&D Sara Kenkare-Mitra, Ph.D., is resigning.
Explore Further
What were the specific reasons behind the failure of latozinemab to meet its primary endpoint in the Phase III INFRONT-3 trial?
What are the differentiating factors or potential advantages of Alector's pipeline assets, such as AL101 and AL137, compared to competitors in Alzheimer's disease treatment?
How does the $700 million partnership with GSK impact Alector's financial outlook and ability to continue developing its remaining pipeline assets?
What are the implications of Alector's layoffs for its future research and development initiatives in neurodegenerative diseases?
What lessons can be learned from the discontinuation of latozinemab and the earlier failed Alzheimer's drug concerning Alector's approach to neurodegenerative drug development?