The results were presented at the 2023 Alzheimer’s Association International Conference (AAIC) being held July 16-20, 2023 in Amsterdam, The Netherlands.
Alzheimer’s disease is the most common neurodegenerative disease and the most common form of dementia, affecting over 30 million people worldwide. It is characterized by progressive memory loss and cognitive decline, with neuropathological accumulation of amyloid plaques, neurofibrillary tangles, and neuroinflammation, ultimately resulting in significant brain atrophy.
ALN-APP is the first clinical-stage program using Alnylam's proprietary C16-siRNA conjugate platform for central nervous system (CNS) delivery and the first investigational RNAi therapeutic to demonstrate gene silencing in the human brain.
The treatment is being developed in collaboration with Regeneron Pharmaceuticals, Inc.
Twenty patients with early-onset Alzheimer’s disease have been enrolled in three single-dose cohorts in Part A of the ongoing phase 1 study.
In this study to date, single doses of ALN-APP, which are administered by intrathecal injection, have shown rapid and robust target engagement with sustained effect over 6 months. In addition, the drug has been well tolerated, with adverse events mild or moderate in severity.
Dr. Sharon Cohen, neurologist and medical director, Toronto Memory Program, said: “We’ve known for decades that mutations that increase APP production, or alter its proteolysis, cause early-onset Alzheimer’s disease, early-onset CAA or both.”
“These Phase 1 results show that a single dose of ALN-APP can rapidly reduce APP production and that this effect is sustained at 6 months. Given the critical need for new and better treatments for AD and CAA, these results are promising, and the approach warrants further study.”
Tim Mooney, director, ALN-APP program leader at Alnylam, added: “The rapid, robust, and sustained target engagement that we have achieved with a single dose of ALN-APP and the encouraging interim safety data to date illustrate the potential of RNAi therapeutics to set a new standard for silencing disease-causing genes in the CNS and target diseases like AD and CAA upstream of existing therapies.”
“We are excited to initiate the multiple dose part of the Phase 1 study and learn more about the potential of this new approach for these devastating diseases.”
Further exploration of single doses of ALN-APP is ongoing in Part A. The safety review committee has also recommended initiation of Part B, the multiple-dose part of the study.
Part B will enroll patients from Part A and has already received regulatory approval to proceed in Canada, where the majority of the Part A clinical trial patients were enrolled.