Alnylam Pharmaceuticals’ investigational RNAi therapeutic has shown promise in patients with early-onset Alzheimer’s disease, according to phase 1 results presented by the company at this year’s Alzheimer’s Association International Conference (AAIC).

Interim results from the early-stage study showed that a single injection of ALN-APP, which is designed to switch off the production of amyloid precursor protein (APP) in the central nervous system, was able to rapidly reduce levels of the protein, with clinical effect sustained over six months.

ALN-APP is being developed in collaboration with Regeneron Pharmaceuticals for both Alzheimer’s disease and the related disorder cerebral amyloid angiopathy (CAA) and is now the first investigational RNAi therapeutic to demonstrate gene silencing in the human brain.

“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,” said Dr Sharon Cohen, neurologist and medical director, Toronto Memory Program.

“Given the critical need for new and better treatments for Alzheimer’s disease and CAA, these results are promising, and the approach warrants further study,” Cohen said.

Further exploration of the single ascending dose portion (part a) of the study is ongoing, Alnylam said, adding that the safety review committee had recommended initiating the multiple-dose phase (part b).

Part b will enrol 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.

Alzheimer’s disease is the most common neurodegenerative disease and the most common form of dementia, affecting over 30 million people worldwide.

Early-onset Alzheimer’s disease, which refers to a subgroup of patients with symptom onset prior to the age of 65, represents approximately 4% to 6% of all cases of the condition.

Tim Mooney, director, ALN-APP programme leader at Alnylam, said: “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 central nervous system and target diseases like Alzheimer’s disease 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.”

Source: pmlive.com