The Medicines Company will pay $25 million to Alnylam Pharmaceuticals as part of an alliance to develop and commercialize Alnylam’s therapeutic program for the treatment of hypercholesterolemia.

Cambridge, Mass.-based Alnylam also could receive up to $180 million in potential development and commercial milestone payments for ALN-PCS RNA interference (RNAi), a gene silencing technology designed to substantially reduce low-density lipoprotein (LDL) cholesterol in patients. Medicines will obtain an exclusive global license to advance the ALN-PCS RNAi therapeutic program.

PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein that regulates LDL receptor levels on hepatocytes; gain-of-function human mutations in PCSK9 are associated with hypercholesterolemia while loss-of-function mutations are associated with lower levels of LDL cholesterol and a reduced risk of cardiovascular disease.

ALN-PCS is a PCSK9 synthesis inhibitor that reduces intracellular and extracellular levels of PCSK9, resulting in lowered plasma levels of LDL cholesterol. MDCO-216 is a naturally occurring variant of a protein found in high-density lipoprotein, or HDL. It is a reverse cholesterol transport agent designed to reduce atherosclerotic plaque burden development and thereby reduce the risk of adverse thrombotic events.

Alnylam’s ALN-PCS program includes ALN-PCS02, an intravenously administered RNAi therapeutic which has completed a Phase I trial, and ALN-PCSsc, a subcutaneously administered RNAi therapeutic currently in preclinical development. Alnylam will continue the program for an estimated one to two years to complete certain preclinical and Phase I clinical studies. Parsippany, N.J.-based Medicines is responsible for leading and funding development from Phase II forward and commercializing the ALN-PCS program if successful.

The two companies have collaborated in the past, most notably on the direct thrombin inhibitor bivalirudin (Angiomax), which was invented by Alnylam CEO John Maraganore, PhD.