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).
In the pivot away from latozinemab, the Bay Area biotech is also laying off 49% of its staff, while the company’s president and head of R&D, Sara Kenkare-Mitra, Ph.D., is resigning effective Dec. 22, Alector announced in an Oct. 22 release.
The INFRONT-3 phase 3 trial had two co-primary endpoints, Alector said, with latozinemab succeeding at reducing plasma progranulin (PGRN) concentrations but failing to slow FTD progression as measured by industry scales. Additionally, the antibody showed no effect on FTD as measured by fluid biomarkers and volumetric magnetic resonance imaging.
Alector had previously said that 119 patients were enrolled in the trial, all of whom have mutated copies of the progranulin gene. Progranulin is a protective compound in the brain, and its absence can lead to neurodegenerative diseases like FTD.
“While latozinemab did not demonstrate a clinical benefit in INFRONT-3, the insights gained are invaluable for understanding progranulin-related neurodegeneration,” Alector's Chief Medical Officer Giacomo Salvadore, M.D., said in the release. “We extend our deepest gratitude to the patients, caregivers and investigators who made this trial possible.”
As a result of the phase 3 miss, Alector is discontinuing the open-label extension of INFRONT-3 and a continuation study of latozinemab, according to the release.
Latozinemab is designed to increase progranulin levels by blocking the activity of sortilin, a protein that shuttles progranulin into the cell’s garbage disposal.
While loss of progranulin has been linked to FTD, “INFRONT-3 indicates restoring PGRN does not translate to clinical benefit in this trial/patient population,” analysts from William Blair wrote in an Oct. 22 note. “While we believe INFRONT-3 data will be a meaningful contribution to the field, we are not surprised to see shares of Alector trading down about 50% after-hours on the news.”
Alector's stock plunged from $3.21 per share at yesterday's market close to $1.56 as of 10:30 a.m. ET on Oct. 22.
With latozinemab on the back burner, Alector is now shifting its focus to another GSK collaboration, this one a phase 2 trial in Alzheimer’s disease called PROGRESS-AD. This study is testing another sortilin-targeting antibody, nivisnebart, in 367 patients with early Alzheimer’s. Enrollment wrapped up in April and Alector intends to complete the trial next year with an interim data analysis in the first half of 2026, according to the Oct. 22 release.
GSK bought into Alector’s progranulin focus in 2021 with a deal worth up to $2.2 billion.
The rest of Alector’s pipeline is wholly owned and preclinical, including an anti-amyloid antibody for Alzheimer’s, an enzyme replacement therapy for Parkinson’s and an siRNA platform, all of which the company is committed to still developing, according to the release.
The recent changes echo Alector's 17% restructure of November 2024, when the AbbVie-partnered Alzheimer’s antibody missed the mark in a phase 2 trial. After the midstage fail, the biotech deprioritized the asset and turned its focus toward the GSK collaboration.