Press release
Alnylam Reports Updated Positive Interim Phase 1 Results for ALN-APP, in Development for Alzheimer’s Disease and Cerebral Amyloid Angiopathy
– First Clinical Study of a Central Nervous System-Administered RNAi Therapeutic Showed Rapid and Robust Target Engagement with Sustained Effect Over 6
About this update from Alnylam Pharmaceuticals, Inc.
[{"type":"text","content":"\n– First Clinical Study of a Central Nervous System-Administered RNAi Therapeutic Showed Rapid and Robust Target Engagement with Sustained Effect Over 6 Months with a Single Dose –\n\n\n– ALN-APP Continues to Demonstrate an Encouraging Clinical Safety and Tolerability Profile –\n\n\n– Multiple-dose Portion of Study, Part B, Being Initiated in Approved Regions –\n\n\n CAMBRIDGE, Mass.--(BUSINESS WIRE)--\nAlnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) announced today updated positive interim results for the ongoing single ascending dose portion of the Phase 1 study of ALN-APP, an investigational RNAi therapeutic targeting amyloid precursor protein (APP) in development for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy (CAA). The results were presented at the 2023 Alzheimer’s Association International Conference (AAIC) being held July 16-20, 2023 in Amsterdam, The Netherlands. 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. ALN-APP is being developed in collaboration with Regeneron Pharmaceuticals, Inc.\n\n\nTwenty 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 been well tolerated. All adverse events were mild or moderate in severity. Cerebrospinal fluid (CSF) white blood cell count and total protein levels showed no remarkable elevations from baseline. Routine laboratory assessments (hematology, serum chemistry, liver function, urinalysis, coagulation) as well as preliminary data for the exploratory biomarker neurofilament light chain (NfL) did not reveal any significant abnormalities. Patients treated with a single dose of 75mg ALN-APP experienced a rapid and sustained reduction in cerebrospinal fluid of both soluble APPα (sAPPα) and soluble APPβ (sAPPβ), biomarkers of target engagement, with maximum reductions of 84% and 90%, respectively. Mean reductions in sAPPα of greater than 55% and sAPPβ greater than 65% were sustained at 6 months after a single dose. Additional results can be seen in the presentation on Capella.\n\n\n“We’ve kno...