Amylyx touts “encouraging” data from Phase 2 Alzheimer’s trial

Treating Alzheimer's patients with combination therapy resulted in a significant reduction in important disease biomarkers.

Neurodegeneration-targeted drug developer Amylyx Pharmaceuticals has announced the publication of promising exploratory analyses from its Phase 2 Alzheimer's trial, showing that its combination therapy could have a significant impact on several pathological pathways associated with neurodegeneration, particularly those involving the tau protein, a key marker of Alzheimer's disease.

The company's investigational drug, AMX0035, is a fixed-dose oral combination of sodium phenylbutyrate and taurursodiol (TURSO) designed to slow or attenuate neurodegeneration by targeting endoplasmic reticulum stress and mitochondrial dysfunction – two key pathways that lead to cell death and neurodegeneration. Preclinical studies have shown that AMX0035 can reduce cell death and improve cell function, with combination therapy demonstrating a synergistic effect. The drug is currently being investigated as a potential treatment for several neurodegenerative diseases.

The Phase 2 PEGASUS study investigated the effects of AMX0035 on cerebrospinal fluid biomarkers in participants with Alzheimer's disease. The results were published in Alzheimer's and dementia: translational research and clinical interventions.

The study's exploratory analyses showed that treatment with AMX0035 resulted in significant reductions in key Alzheimer's disease biomarkers, particularly phosphorylated tau181 and total tau, both of which are directly related to the pathology of the disease. In addition, AMX0035 reduced levels of biomarkers associated with synaptic and neuronal degeneration, including neurogranin and fatty acid binding protein-3, as well as a biomarker of gliosis, YKL-40.

“Alzheimer's disease is characterized by amyloid plaques and tau fibrils, but it is now known that these pathologies are accompanied by alterations in several cellular and molecular pathways, including neuronal dysfunction, neurodegeneration and oxidative stress, that drive the progression of this relentless disease,” said Steven E. Arnold, MD, Professor of Neurology at Harvard Medical School. “The results of this exploratory analysis suggest that AMX0035 affects key pathways involved in the pathogenesis of Alzheimer's disease and other neurodegenerative diseases.”

“These data support the preclinical and clinical evidence that AMX0035 has the potential to treat neurodegenerative diseases associated with tau dysfunction and tau aggregation,” said Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx.

Photo: Amylyx Pharmaceuticals