Alnylam and Regeneron Achieve Human Proof-of-Concept for ALN-APP RNAi Therapy in Alzheimer’s Disease and Cerebral Amyloid Angiopathy

Intelligent Finance APP learned on April 27 that Alnylam (ALNY.US) and Regeneron (REGN.US) announced positive interim results from the first human clinical trial of their investigational RNAi therapy, ALN-APP. ALN-APP is an RNAi therapy targeting amyloid precursor protein (APP) for the treatment of Alzheimer's disease and cerebral amyloid angiopathy (CAA). The trial results showed that ALN-APP not only demonstrated good safety and tolerability but also rapidly and persistently reduced APP-related biomarkers in cerebrospinal fluid with a single dose, with the highest dose reducing levels by up to 90%.

It is reported that several RNAi therapies have already received FDA approval for the treatment of rare or specialized diseases, becoming an innovative treatment model recognized by the industry. The C16 conjugation technology platform developed by Alnylam is specifically optimized for delivery to CNS tissues. By conjugating different lipid molecules to RNAi and adjusting their lipophilicity, this system has already demonstrated significant mRNA expression reduction across a wide range of CNS tissues in rat and non-human primate models.

ALN-APP is an RNAi therapy that applies C16 conjugation technology to target the mRNA encoding the APP protein. It can degrade mRNA and reduce the expression of the APP protein. Mutations in the APP gene are a significant cause of early-onset Alzheimer's disease and cerebral amyloid angiopathy, and amyloid plaque deposition is one of the hallmark features in the brains of Alzheimer’s patients.

At the same time, patients receiving ALN-APP treatment showed a rapid and sustained reduction in soluble APPα (sAPPα) and APPβ (sAPPβ) in cerebrospinal fluid in a dose-dependent manner. The maximum reductions were 84% and 90%, respectively. In patients receiving the highest dose of ALN-APP treatment, the levels of the two biomarkers decreased by an average of more than 70% and lasted for at least three months.