Alector’s AbbVie-partnered Alzheimer's disease asset has failed to slow disease progression in a phase 2 study, the latest in a string of investigational meds missing the mark in the indication.
The California-based biotech is stopping a related long-term extension study and laying off 17% of its workforce, according to a Nov. 25 post-market release. The company's stock has dropped 35% since the release was posted, down from $3.96 per share to $2.59 as of 1 p.m. ET on Nov. 26. Mizuho analysts deemed the data outcome "a significant setback," but said more time was needed to fully evaluate the long-term impact.
Alector assessed AL002—a monoclonal IgG1 antibody designed to activate the TREM2 protein—in a trial of 381 individuals with early Alzheimer's. The placebo-controlled study, dubbed INVOKE-2, failed to hit the primary goal of slowing disease progression as measured by a dementia severity scale.
When looking at secondary clinical and functional endpoints, no favorable treatment effects were tied to AL002, according to Alector, which didn't drill into the data. There also weren’t any significant beneficial effects on Alzheimer’s fluid biomarkers associated with the investigational therapy, plus PET imaging didn’t show any treatment-related reduction of amyloid levels in the brain.
If that wasn't enough to sink AL002's prospects, MRI changes resembling amyloid-related imaging abnormalities (ARIA) and infusion-related reactions were observed in INVOKE-2. ARIA suggests a risk of brain bleeds or swelling and is a primary concern for the class of amyloid medicines.
“With a robust dataset from the INVOKE-2 trial, we plan to further explore TREM2 biology,” Alector Chief Medical Officer Gary Romano, M.D., Ph.D., said in the company release. “We plan to share the results of the trial with the scientific community in the near future in the hopes of contributing to the understanding of AD pathophysiology and advancing effective therapeutics for this terrible disease.”
Back in 2017, AbbVie paid Alector $205 million upfront to co-develop new treatments for Alzheimer’s—namely AL002 and another candidate called AL003. But the Big Pharma ended part of the collaboration in 2022 after viewing phase 1 data for AL003 in healthy volunteers.
Alector removed AL003 from its pipeline but continued work with AbbVie on AL002. Across both AL002 and AL003, the deal was worth up to $985.6 million in option exercise and milestone payments, with only paydays tied to AL002 remaining after the AL003 portion was axed.
In the wake of yesterday's results, Alector is now prioritizing its GSK-partnered programs, which include monoclonal antibody latozinemab. Top-line data from a pivotal phase 3 trial of latozinemab in frontotemporal dementia with a progranulin gene mutation is expected in late 2025 or early 2026.
In efforts to “align resources” with the company’s strategic priorities, the biotech is trimming its workforce by about 17%, which equates to about 41 workers, according to Securities and Exchange Commission filings.
As of Sept. 30, Alector had $457.2 million in cash and investments on hand, money the company believes will fund operations through 2026.
Alector’s trial failure was reported just hours after Cassava Sciences shared that its filamin A-targeting drug had missed the co-primary endpoints in a phase 3 Alzheimer's trial, and mere weeks after UCB reported the failure of its anti-tau antibody bepranemab to improve cognition and function.
This story was updated at 1 p.m. ET on Nov. 26 to include stock information and analysis.