Alnylam Pharmaceuticals and Regeneron Pharmaceuticals have reported positive interim data from the ongoing single ascending dose portion of the Phase l trial of ALN-APP to treat Alzheimer’s disease.
Part A of the trial included 20 patients with early-onset Alzheimer’s disease in three single-dose cohorts.
Single doses of ALN-APP, which are given through intrathecal injection, have so far been well tolerated.
Patients experienced mild or moderate adverse events. The available cerebrospinal fluid data for white blood cells and protein were also found to be similar to placebo.
Initial results for neurofilament light chain from a subset of cohorts appeared comparable to placebo.
The interim data also showed that patients who received ALN-APP experienced dose-dependent, rapid and sustained decrease in cerebrospinal fluid of both soluble APPα (sAPPα) and APPβ (sAPPβ), with a maximum reduction of 84% and 90%, respectively.
The median reduction of both biomarkers of more than 70% was sustained for at least three months at the highest dose evaluated.
Furthermore, the initial results establish the first human translation of Alnylam’s proprietary C16-siRNA conjugate platform for central nervous system (CNS) delivery.
The results also mark the first clinical demonstration of gene silencing in the human brain using an RNAi therapeutic.
ALN-APP is currently under development as an RNAi therapeutic targeting amyloid precursor protein (APP) for Alzheimer’s disease and cerebral amyloid angiopathy CAA.
Alnylam chief medical officer Pushkal Garg said: “ALN-APP, via its upstream targeting mechanism, has the potential to address the underlying cause of two devastating CNS diseases, Alzheimer’s disease and CAA, which affect many millions of people and their families around the world.
“Thus, we are excited by these interim clinical data for ALN-APP, which demonstrate rapid, substantial and sustained target protein reduction and encouraging safety and tolerability to date.”
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