Raphael Thys
Treating Alzheimer’s patients with combination therapy led to significant reductions in key disease biomarkers.
Neurodegeneration-targeting drug developer Amylyx Pharmaceuticals has announced the publication of promising exploratory analyses from its Phase 2 Alzheimer’s trial, which shows its combination therapy may have a significant impact on multiple pathological pathways related to neurodegeneration, particularly those involving tau protein, a key marker of Alzheimer’s disease.
The company’s investigational drug, AMX0035, is an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol (TURSO), designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum stress and mitochondrial dysfunction – two central pathways that lead to cell death and neurodegeneration. Preclinical studies demonstrated that AMX0035 may reduce cell death and improve cellular function, with the combination therapy showing a synergistic effect, and the drug is currently under investigation as a potential treatment for various neurodegenerative diseases.
The Phase 2 PEGASUS trial investigated the effects of AMX0035 on cerebrospinal fluid biomarkers in participants with Alzheimer’s disease, and the findings have been published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions.
The exploratory analyses from the trial demonstrated that treatment with AMX0035 led to significant reductions in key Alzheimer’s disease biomarkers, particularly phosphorylated tau181 and total tau, both of which are directly associated with the disease’s pathology. Additionally, AMX0035 reduced levels of biomarkers linked to synaptic and neuronal degeneration, including neurogranin and fatty acid binding protein-3 and a biomarker of gliosis, YKL-40.
“Alzheimer’s disease is defined by amyloid plaques and tau tangles, but it’s now understood that these pathologies are accompanied by alterations in multiple cell and molecular pathways, including neuronal dysfunction, neurodegeneration, and oxidative stress, driving the progression of this relentless disease,” said Dr Steven E Arnold, MD, Professor of Neurology at Harvard Medical School. “The results from this exploratory analysis suggest that AMX0035 engages important pathways implicated in the pathogenesis of Alzheimer’s disease and other neurodegenerative diseases.”
“These data lend further support to the preclinical and clinical evidence that AMX0035 has the potential to treat neurodegenerative diseases associated with tau dysfunction and tau aggregation,” said Dr Camille L Bedrosian, Chief Medical Officer at Amylyx.
Photograph: Amylyx Pharmaceuticals