The Medicines Company has initiated study sites, and begun enrolling patients, in the ORION-1 phase 2 study. ORION-1 will compare the effects of differenct ALN-PCSsc doses given as subcutaneous injections in a quarterly or bi-annual dosing regimen in patients with atherosclerotic cardiovascular disease (ASCVD) or risk equivalent ASCVD and elevated LDL-C.
ALN-PCSsc is an investigational RNA interference (RNAi) therapeutic targeting PCSK9, a genetically validated protein regulator of LDL receptor metabolism. In contrast to anti-PCSK9 monoclonal antibodies (MAbs) that bind to PCSK9 in blood, ALN-PCSsc is a first-in-class investigational medicine that acts by turning off PCSK9 synthesis in the liver, according to a press release from The Medicine Company.
The ORION-1 study is a Phase 2, placebo-controlled, double-blind, randomised trial in 480 subjects with atherosclerotic cardiovascular disease or ASCVD-risk equivalents (such as diabetes, familial hypercholesterolemia) and elevated LDL-C despite maximum tolerated doses of LDL-C lowering therapies to evaluate the efficacy, safety, and tolerability of ALN-PCSsc injection(s).
“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,” says John JP Kastelein, professor of Medicine, Department of Vascular Medicine at the Academic Medical Center, University of Amsterdam, Netherlands, and chairman of the Executive Committee for ORION-1. “We look forward to the expected completion of this phase 2 trial by the end of 2016 to confirm what may be an advantageous dosing regimen for patients at risk for cardiovascular events due to elevated LDL-C.”
“We are very pleased with the rapid development progress for ALN-PCSsc, which has moved from phase 1 to phase 2 in a few weeks,” says Clive Meanwell, chief executive officer, The Medicines Company. “We remain very excited about the prospects of having a bi-annual dosing treatment available for LDL-C reduction which has the potential to improve adherence and address a major unmet medical need.”
“We are pleased to have successfully completed the transition of ALN-PCSsc to our partners at The Medicines Company,” says John Maraganore, chief executive officer of Alnylam Pharmaceuticals, Inc. “We look forward to providing all necessary support to enable MDCO efforts, including in areas such as regulatory and manufacturing.”
The Medicines Company and Alnylam Pharmaceuticals are collaborating in the advancement of ALN-PCSsc per the companies’ agreement formed in early 2013. Under the terms of the agreement, Alnylam completed certain pre-clinical studies and the phase 1 clinical study, with The Medicines Company leading and funding the development of ALN-PCSsc from phase 2 forward as well as potential commercialisation.