Alnylam reports added ‘positive interim results’ from Phase 1 Alzheimer’s trial

Alnylam Pharmaceuticals (ALNY) announced what it calls “additional 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 in development for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy, or CAA. The data were presented today in a late-breaker session at the 16th Clinical Trials on Alzheimer’s Disease, or CTAD, conference, being held October 24-27 in Boston, MA. ALN-APP is the first clinical-stage program using Alnylam’s proprietary C16-siRNA conjugate platform for central nervous system delivery and the first investigational RNAi therapeutic to demonstrate gene silencing in the human brain, the company said. ALN-APP is being developed in collaboration with Regeneron (REGN). Twenty patients have been enrolled in three single-dose cohorts in Part A of the ongoing Phase 1 study in patients with early-onset Alzheimer’s disease. In this study to date, blinded single doses of ALN-APP, which are administered by intrathecal injection, have been well tolerated. All adverse events were mild or moderate in severity. Cerebral spinal fluid (CSF) safety biomarkers, routine labs, and the exploratory biomarker neurofilament light chain (NfL) all continue to show no concerning trends. Patients treated with a single dose of 75mg ALN-APP experienced rapid and sustained reduction in CSF of both soluble APPalpha and soluble APPbeta, biomarkers of target engagement, with maximum reductions of 84% and 90%, respectively. These effects were highly durable, with mean reductions in sAPPalpha and sAPPbeta of 33% and 39%, respectively, at 10 months after a single 75mg dose. Further exploration of single doses of ALN-APP is ongoing in Part A. In addition, the first patient has now been dosed in Part B, the multiple-dose part of the study. Part B was previously initiated in Canada and has also now received all required approvals to proceed in the UK and the Netherlands. The multiple dose part of the study remains on partial clinical hold in the U.S. due to findings observed in non-clinical chronic toxicology studies.