(By Balaseshan S) Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) announed encouraging results from its initial-stage trial of ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of severe hypercholesterolemia, a disorder characterized by too much cholesterol in the body.
The company said the results of initial-stage trial of RNAi therapeutic targeting the gene proprotein convertase subtilisin/kexin type 9 (PCSK9) showed durable reductions of PCSK9 plasma levels of up to 84% and lowering of low-density lipoprotein cholesterol (LDL-C), or "bad" cholesterol, of up to 50%.
The new data also highlight continued improved efficacy and tolerability for Alnylam's second-generation lipid nanoparticle (LNP) delivery technology. The data were presented at the American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology 2012 Scientific Sessions held in Chicago.
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ALN-PCS is a PCSK9 synthesis inhibitor that reduces intracellular and extracellular levels of PCSK9 resulting in lowered plasma levels of LDL-C.
Results showed that administration of a single dose of ALN-PCS, in the absence of concomitant lipid-lowering agents such as statins, resulted in statistically significant and durable reductions of PCSK9 plasma levels of up to 84% and lowering of LDL-C of up to 50%.
Importantly, ALN-PCS demonstrated consistent clinical activity toward both PCSK9 and LDL-C independent of baseline levels of PCSK9, highlighting the unique mechanism of action for a PCSK9 synthesis inhibitor.
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ALN-PCS was shown to be safe and well tolerated in this study and there were no serious adverse events related to study drug administration. There were no drug-related discontinuations and no liver enzyme elevations.
There was also no significant change compared to baseline in levels of high-density lipoprotein (HDL), or "good" cholesterol, consistent with the phenotype observed in human PCSK9 loss-of-function mutations.
The Phase 1 study was conducted as a randomized, single-blind, placebo-controlled, single-ascending dose study in healthy volunteer subjects with elevated baseline LDL-C (greater than 116mg/dL).
The primary objective of the study was to evaluate the safety and tolerability of a single dose of ALN-PCS. A total of 32 subjects were enrolled into six sequential dose cohorts ranging from 0.015 to 0.400 mg/kg in a 3:1 randomization of drug to placebo.
ALN-PCS is an RNAi therapeutic that utilizes proprietary second-generation LNP technology with the MC3 lipid. This study represents the first human results with this delivery platform. The same RNAi delivery formulation is being used for Alnylam's ALN-TTR02 program, an RNAi therapeutic targeting TTR for the treatment of ATTR.
Severe 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.
ALN-PCS is a systemically delivered RNAi therapeutic targeting the gene proprotein convertase subtilisin/kexin type 9 (PCSK9), a target validated by human genetics that is involved in the metabolism of LDL-C. Alnylam intends to partner its ALN-PCS program prior to initiating a Phase 2 clinical study.
ALNY is trading up 5.00% at $10.50 on Friday. The stock has been trading between $5.88 and $13.75 for the past 52 weeks.