Alnylam
Pharmaceuticals, Inc. (Nasdaq: ALNY), a
leading RNAi therapeutics company, announced today positive results from
its Phase I clinical trial of ALN-PCS, an RNAi therapeutic targeting
PCSK9 for the treatment of severe hypercholesterolemia. ALN-PCS is a
PCSK9 synthesis inhibitor that reduces intracellular and extracellular
levels of PCSK9 resulting in lowered plasma levels of low-density
lipoprotein cholesterol (LDL-C), or "bad" cholesterol. The new data were
presented at the American Heart Association's Arteriosclerosis,
Thrombosis and Vascular Biology 2012 Scientific Sessions held in
Chicago. 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%. The new
data also highlight continued improved efficacy and tolerability for
Alnylam's second-generation lipid nanoparticle (LNP) delivery technology.
"We are very excited by these new ALN-PCS data that demonstrate robust
clinical efficacy for this PCSK9 synthesis inhibitor. Indeed, we believe
the unique mechanism of action for ALN-PCS, which inhibits the synthesis
of PCSK9 in liver cells thereby reducing both its intracellular and
extracellular functions, provides a differentiated strategy for PCSK9
antagonism. This mechanism of action for ALN-PCS results in potent and
durable LDL-C reductions and consistent clinical activity across a wide
range of baseline PCSK9 plasma levels, including individuals with very
high PCSK9 levels," said Akshay K. Vaishnaw, M.D., Ph.D., Senior Vice
President and Chief Medical Officer of Alnylam. "These new results show
very robust, statistically significant, and dose-dependent lowering of
both PCSK9 and LDL-C levels in a single dose study performed in the
absence of statin co-administration. In addition, ALN-PCS treatment was
well tolerated at all dose levels studied to date indicating the
potential to even further dose escalate in future studies."
"Cardiovascular disease remains the leading cause of mortality
worldwide, with elevated LDL-C a major modifiable risk factor. A
substantial number of patients cannot achieve target LDL levels with
current drugs, such as statins, and it is clear that new therapeutic
options are needed," said Daniel J. Rader, M.D., Director of Preventive
Cardiovascular and Associate Director of the Institute for Translational
Medicine and Therapeutics at University of Pennsylvania. "As a key
regulator of the LDL receptor, liver-expressed PCSK9 is one of the most
important and best validated new targets in molecular medicine for the
treatment of hypercholesterolemia. An RNAi therapeutic targeting PCSK9
expression in the liver has the potential to rapidly and durably lower
LDL cholesterol, thereby reproducing the effects observed in
loss-of-function human mutations that are associated with significant
clinical benefit. I am very encouraged by the ALN-PCS data generated to
date and look forward to continued studies that highlight the unique
mechanistic approach of PCSK9 synthesis inhibitors, including the
potential magnitude and durability of LDL-C response when ALN-PCS is
co-administered with statins."
The Phase I 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. Secondary objectives of the
study included assessment of pharmacodynamic effects of the drug on
plasma PCSK9 protein levels and evaluation of clinical efficacy as
measured by LDL-C levels. 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.