Alnylam and Regeneron have reported positive interim results from their Phase 1 trial of ALN-APP in patients with early-onset Alzheimer’s disease (AD), showing a reduction in AD biomarkers with no severe adverse events. ALN-APP is a novel “gene silencing” therapeutic that targets the amyloid precursor protein (APP) at an early stage of processing. Accumulation of amyloid plaques in the brain is one of the pathological hallmarks of AD, and an early event in both AD and cerebral amyloid angiopathy (CAA), which denotes the build-up of amyloid in the walls of blood vessels in the brain.
The Phase 1 study of ALN-APP is a multi-center, randomised, double-blind and placebo-controlled trial which is aiming to enrol 60 participants with early-onset AD at study sites in Canada, the Netherlands, the UK and USA. ALN-APP is delivered via intrathecal injection (injection into the spinal canal) and the interim results reported by Alnylam and Regeneron come from part A of their clinical trial, in which participants received a single dose of ALN-APP. In a press release published earlier this month, Alnylam and Regeneron explained that ALN-APP was well-tolerated by study participants, with no severe adverse events reported to date.
Participants showed a dose-dependent and rapid reduction in the levels of soluble APP in cerebrospinal fluid samples, with reductions of up to 90% compared to placebo. On average, a 70% reduction in the APP biomarkers was sustained for at least 3 months at the highest ALN-APP dose tested, indicating that the drug is effectively targeting APP. Studies are ongoing and the companies are planning to report detailed interim results at an upcoming scientific conference. Read the press release: https://investors.alnylam.com/press-release?id=27441