Trial of investigational PCSK9 synthesis inhibitor for atherosclerotic CVD underway

A new study will compare the effects of different doses of an investigational RNA interference therapeutic that targets PCSK9 given as subcutaneous injections in a quarterly or bi-annual dosing regimen in patients with atherosclerotic CVD and elevated LDL.

ORION-1 is a phase 2, placebo-controlled, double blind, randomized trial with a target enrollment of 480 patients with atherosclerotic CVD (ASCVD), or ASCVD risk equivalents such as diabetes and familial hypercholesterolemia, and elevated LDL despite maximally tolerated doses of LDL-lowering therapies. The goal is to evaluate the efficacy, safety and tolerability of ALN-PCSsc, an RNA interference therapeutic targeting PCSK9, administered via injection, according to a press release issued by The Medicines Company. In contrast to anti-PCSK9 monoclonal antibodies that bind to PCSK9 in blood, ALN-PCSsc is a first-in-class investigational therapy that acts by turning off PCSK9 synthesis in the liver, according to the release.

The Medicines Company has initiated study sites and begun enrollment, as of January, according to the release.

“The results from the phase 1 study of ALN-PCSsc were impressive, and we are excited to see the rapid progression of this therapy into the next phase of its development,” John J.P. Kastelein, MD, PhD, professor of medicine, department of vascular medicine, Academic Medical Center of the University of Amsterdam, stated in the release. Kastelein is chairman of the executive committee for ORION-1.

The phase 2 trial is expected to be completed by the end of 2016, according to information in the release.

In accordance with a 2013 agreement made with The Medicines Company in the advancement of ALN-PCSsc, Alnylam Pharmaceuticals completed preclinical studies and the phase 1 clinical study, according to the release.

Disclosure: Kastelein is chairman of the executive committee for the ORION-1 trial.