Hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood which is known to increase the risk of coronary artery disease, the leading cause of death in the U.S.
Some forms of hypercholesterolemia can be treated through dietary restrictions, lifestyle modifications (e.g., exercise and smoking cessation) and medicines such as statins. However, a large proportion of patients with hypercholesterolemia are not achieving target LDL cholesterol (or ‘bad’ cholesterol) goals with statin therapy, including familial hypercholesterolemia patients, acute coronary syndrome patients, high-risk patient populations (e.g., patients with coronary artery disease, diabetics, symptomatic carotid artery disease, etc.) and other patients that are statin intolerant. Severe forms of hypercholesterolemia are estimated to affect more than 500,000 patients worldwide, and as a result, there is a significant need for novel therapeutics to treat patients with hypercholesterolemia whose disease is inadequately managed by existing therapies.
Our collaborators at The Medicines Company are advancing clinical development of ALN-PCSsc, an investigational RNAi therapeutic targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) that utilizes our Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform
, enabling subcutaneous dosing with increased potency and durability, and a wide therapeutic index
Inhibition of PCSK9 synthesis through an RNAi mechanism has the potential to lower tissue and circulating plasma PCSK9 protein levels resulting in higher expression of LDL receptor in the liver, and consequently lower LDL cholesterol levels in the blood stream. Lower LDL cholesterol is associated with a decreased risk of cardiovascular disease, including myocardial infarction and stroke. ALN-PCSsc is an investigational PCSK9 synthesis inhibitor that lowers levels of both intracellular and extracellular PCSK9, thereby phenocopying the human genetics observed in loss of function or null human PCSK9 mutations (N. Engl. J. Med. (2006) 354:1264-1272; Am. J. Hum. Genet. (2006) 79: 514-523). Further, RNAi therapeutics can block PCSK9 synthesis across a wide range of plasma PCSK9 levels, which are known to vary widely amongst individuals and are also elevated in association with statin therapy.
In February 2013, we formed an exclusive global alliance with The Medicines Company for the development and commercialization of the ALN-PCSsc program. Alnylam led the program through the completion of Phase 1 and The Medicines Company is responsible for leading and funding development from Phase 2 forward and commercializing the ALN-PCSsc program if successful.
Please read the latest press releases and data presentations for ALN-PCSsc here.