GSK and Alector have stopped a phase 2 trial of their Alzheimer’s disease drug candidate after an interim analysis found the study was unlikely to hit its primary endpoint.
The study randomized 367 people with early Alzheimer’s to receive one of two doses of the anti-sortilin 1 antibody nivisnebart or placebo. GSK and Alector bet that downregulating the sortilin receptor would elevate levels of progranulin, a protein that supports neurons and microglia in the brain, and thereby improve outcomes in Alzheimer’s.
However, a futility analysis found the phase 2 study was unlikely to meet its primary endpoint of slowing disease progression at completion. GSK and Alector responded by stopping the trial and working with investigators to get the news to participants.
The result effectively ends Alector’s partnership with GSK, TD Cowen analysts said in a note to investors. GSK paid $700 million upfront to partner with Alector in 2021, securing the right to co-develop two drug candidates. Both molecules have failed key clinical trials in the past six months.
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Latozinemab, another antibody designed to boost progranulin by blocking sortilin, failed a phase 3 trial in frontotemporal dementia last year. TD Cowen analysts said latozinemab’s failure and discontinuation “led to skepticism about the viability of targeting progranulin.” The discontinuation of the phase 2 trial of nivisnebart, a molecule with the same mechanism as latozinemab, was expected, the analysts said.
The setbacks follow the failure of Alector’s AbbVie-partnered Alzheimer’s prospect in 2024. That drug candidate was designed to activate TREM2, a microglial receptor that genetic and preclinical research suggests plays a central role in Alzheimer’s.
TREM2 and progranulin are “exciting targets for microglial activation and neuroprotection,” William Blair analysts said in their own note to investors April 29. While the analysts had been “energized” by the scientific rationale, they said central nervous system penetration of the antibody-based agonists in humans remains an open question. A recent presentation of latozinemab data raised the question again, the analysts said.
Alector’s next wave of assets uses technology for crossing the blood-brain barrier. The biotech plans to file to test an anti-amyloid beta antibody that uses the technology in humans in the first quarter of next year. TD Cowen analysts said preclinical data on the technology are “initially promising,” but cautioned that clinical data “remain distant.”
