Shifting Paradigms in Alzheimer’s Research
On December 12, Alzheimer’s trials involving Novo Nordisk’s blockbuster GLP-1 drug semaglutide, despite their setbacks, highlight a growing trend towards viewing Alzheimer’s disease as a complex interplay of various pathways—similar to modern cancer therapies, according to experts.
Currently, there are just two approved drugs for slowing Alzheimer’s: Eli Lilly’s Kisunla and Eisai’s Leqembi. Both have shown potential to delay the disease’s progress by around 30% by targeting toxic amyloid plaques. However, there’s an ongoing effort to explore additional targets and strategies for better outcomes.
An estimated 55 million people worldwide live with dementia, with about 60% of those cases attributable to Alzheimer’s, characterized by amyloid and tau protein build-up in the brain. Howard Fillit of the Alzheimer’s Drug Discovery Foundation remarks, “All diseases of aging require combination therapy; focusing on just one pathway won’t be sufficient.”
Recently, some analyses have suggested that Black patients may experience different forms of the disease, suggesting that single-target treatments might fall short. Additionally, research suggests that men may respond better to certain treatments than women, and patients with lower levels of tau have shown improved results.
The shift towards personalized treatment options reflects a broader trend seen in cancer therapy, which has evolved significantly over the past two decades from generic methods to more precise, targeted approaches. David Watson, CEO of the Alzheimer’s Research and Treatment Center, states, “Current research feels akin to oncology from 20 years ago… it’s incredibly exciting.”
Novo’s findings indicate a pivotal transition towards drug development strategies that target various biological factors related to Alzheimer’s. However, it’s worth noting that while oral semaglutide showed no cognitive benefits for early Alzheimer’s patients, more data—including patient characteristics that could shed light on the treatment’s efficacy—will be shared in March.
Both Kisunla and Leqembi will require careful monitoring due to potential side effects like brain swelling, and trials are underway for individuals with asymptomatic Alzheimer’s. Interim results might emerge as soon as 2027. Eli Lilly emphasizes that early treatment may yield better outcomes but continues to expand its focus primarily on therapies for substance use disorders.
Targeting Multiple Pathologies
Brooks noted that the research landscape is evolving rapidly, with a notable push towards drugs that address tau and other complications associated with mixed dementia, as many patients may not only have Alzheimer’s. Biogen is also set to release data next year on a novel tau-targeting drug after a recent failure by another company in this area.
On a related note, Roche’s new drug, trontinemab, aims to efficiently cross the blood-brain barrier and is expected to result in better outcomes than current treatments, particularly for individuals genetically predisposed to adverse effects from existing therapies.
Meanwhile, Annovis Bio is advancing a multi-target drug, buntanetap, currently in phase three trials, which successfully addressed issues of participant eligibility in earlier studies, showing significant improvement in cognitive functions after refining its criteria.
In conclusion, the Alzheimer’s research landscape is increasingly complicated but ripe with potential, as the traditional models of treatment are re-evaluated for efficiency and effectiveness in combating this challenging cognitive condition.
