Alnylam, Medicine's Company Start Phase 1 Trial Of ALN-PCSsc In Hypercholesterolemia
By Cyndi Root
Alnylam Pharmaceuticals and The Medicines Company announced that they have begun a Phase 1 trial of ALN-PCSsc for the treatment of hypercholesterolemia. The companies announced the trial initiation in a press release, stating that the trial has triggered a milestone payment from The Medicine’s Company to Alnylam. The companies intend to report data from the trial in mid-2015. David Kallend, VP at The Medicines Company, said, “Based on its mechanism of action and pre-clinical results, we believe that ALN-PCSsc has a highly competitive profile as compared with anti-PCSK9 monoclonal antibodies and a potential for a less frequent, small volume dosing regimen, and we look forward to confirming this potential in the clinic.”
Alnylam and The Medicines Company Agreement
Alnylam and The Medicines Company formed their partnership in early 2013, agreeing to advance ALN-PCSsc through the development process. Alnylam is responsible for pre-clinical studies and the Phase 1 clinical study of ALN-PCSsc. If positive results are found in the Phase 1 trial, The Medicines Company will lead development from Phase 2 forward through regulatory filings and commercialization.
ALN-PCSsc
ALN-PCSsc is an RNAi therapeutic, administered subcutaneously. It targets the gene proprotein convertase subtilisin/kexin type 9 (PCSK9), which is involved in low-density lipoprotein cholesterol (LDL-C) metabolism. The agent is engineered from Alnylam’s proprietary GalNAc conjugate delivery platform and its ESC-GalNAc technology. The company states that a once-monthly or once-quarterly, low volume subcutaneous dose may be effective.
The Phase 1 trial of ALN-PCSsc is a placebo-controlled trial of 76 people in the U.K. Enrolled patients will have an elevated baseline LDL-C of greater-than or equal to 100 mg/dL. In the first phase of the study, patients will receive a single ascending dose (SAD) phase. In the second phase, patients will receive a multiple dose (MD) consisting of two subcutaneous doses of either ALN-PCSsc or placebo. Safety and tolerability are the primary endpoints, while secondary endpoints include reductions of plasma PCSK9 levels and serum LDL-C levels.
In previously published studies, Alnylam and collaborators have shown that ALN-PCS02 administration lowers plasma PCSK9 up to 84 percent relative to baseline and placebo. Additionally, serum levels are reduced up to 57 percent. The effects were durable, lasting for weeks after a single dose, and the drug was well tolerated.