Alnylam Pharmaceuticals said this week that it has begun dosing patients in a previously announced phase I study of its siRNA-based hypercholesterolemia drug ALN-PCS.
ALN-PCS comprises siRNAs against proprotein convertase subtilisn/kexin type 9, which has been shown to regulate low-density lipoprotein receptor levels and play a role in plasma LDL clearance. It incorporates a second-generation lipid nanoparticle technology called MC3.
The phase I study is being conducted in the UK and is designed to test single, escalating doses of the drug in up to 32 healthy volunteers with elevated baseline low-density lipoprotein levels.
“The primary objective of the study is to evaluate the safety and tolerability of a single dose of ALN-PCS, with patients being enrolled into five sequential cohorts of increasing doses ranging from 0.015 to 0.25 mg/kg,” Alnylam said. “Secondary objectives include characterization of plasma and urine pharmacokinetics of ALN-PCS, and assessment of pharmacodynamic effects of the drug on plasma PCSK9 protein and LDLc levels measured from serial blood samples prior to and following dosing.”