AZN buys private company Alphacore for an undisclosed sum.
uk.finance.yahoo.com
Interesting lead product:
October 9, 2012 (Ann Arbor, MI) — AlphaCore Pharma, announced today that results from the
company’s Phase 1 clinical trial have met the primary endpoint by demonstrating the safety and
tolerability of the drug ACP-501 (recombinant human LCAT).
ACP-501 also met the study’s secondary endpoints by rapidly and substantially elevating HDL
cholesterol, often referred to as “good” cholesterol. The elevation of HDL cholesterol was due entirely to
an increased formation of cholesteryl esters. This represents an increase in the unidirectional movement
of tissue cholesterol, an important breakthrough in the development of a reverse cholesterol transport
(RCT) therapy. RCT is the process by which cholesterol in the arterial wall is transported to the liver for
excretion from the body.
“We are gratified that ACP-501 was shown to be safe in this trial, and moreover, that the changes in
biomarkers are consistent with rapid enhancement of reverse cholesterol transport”, stated Bruce
Auerbach, President of AlphaCore. ”The increase in HDL cholesterol after administration of ACP-501
supports the notion that LCAT is a bottleneck in the reverse cholesterol transport process.” noted
Auerbach.
The Phase 1 single ascending dose study evaluated 16 volunteers with stable atherosclerosis. Four
subjects in each of four cohorts were administered a single intravenous infusion of ACP-501 and followed
for 28 days. No serious adverse events were reported for ACP-501. The study site was the National
Heart, Lung and Blood Institute (NIH) and investigators included Robert D. Shamburek, MD (Principal
Investigator), Alan Remaley, MD and Marcelo Amar, MD.
ACP-501 is the first enzyme supplementation strategy targeting acute plaque stabilization. The data from
this study support ongoing clinical development of ACP-501 in patients with high-risk atherosclerosis,
including acute coronary syndromes.
About Reverse Cholesterol Transport (RCT)
Cholesterol must be removed from peripheral tissues or it will accumulate and cause disease.
Cholesterol is removed from tissues and delivered to the liver for excretion from the body by a multistep
process known as “Reverse Cholesterol Transport.” In the first step of RCT, small high-density
lipoprotein particles (HDL3) in the bloodstream acquire cholesterol from tissues by a process known as
“cholesterol efflux”. In the second step, the enzyme lecithin: cholesterol acyltransferase (LCAT) converts
the effluxed cholesterol to cholesteryl ester. This newly formed cholesteryl ester moves from the HDL
surface into the core of the HDL particle, and allows the maturation of HDL from small HDL3 to large
HDL2. In the third step of RCT the LCAT-derived cholesteryl esters in HDL2 are either transferred to LDL
in exchange for triglyceride, or removed directly by the liver via scavenger receptor-B1. LDLs are
removed from the circulation by the classical LDL receptor pathway. Once in the liver the cholesteryl
esters from both the LDL and HDL are hydrolyzed back to cholesterol, which can then be converted to
bile acids or excreted as cholesterol into bile.
The ability of LCAT to drive cholesterol removal has been demonstrated in several animal species, most
notably in rabbits, a species that shares many common steps of RCT with humans. In rabbits the over-
expression of LCAT through genetic manipulation or the injection of recombinant LCAT, results in HDL
cholesterol elevation and, more importantly, increases RCT and reduces cholesterol accumulation in
arteries.
About ACP-501
ACP-501 is a recombinant human lecithin:cholesterol acyltransferase (rhLCAT), an enzyme in the
bloodstream that participates in the RCT process. ACP-501 is under development as a therapy for acute
coronary syndromes, and other high-risk atherosclerosis conditions for the rapid removal of tissue
cholesterol. AlphaCore Pharma’s approach to stimulating the flux through the RCT pathway is distinct
from other HDL therapies developed to date. ACP-501 acts directly upon existing small HDL particles,
which are already in abundance, and matures them into larger, cholesteryl ester-rich HDL particles, which
are then ready for elimination from the body.
ACP-501 is also being developed to treat familial LCAT deficiency, as an orphan-designated enzyme
replacement therapy, and other conditions where LCAT activity is low.
About AlphaCore Pharma
AlphaCore Pharma is a privately held Ann Arbor-based biotechnology company formed in 2007 to
develop recombinant human LCAT as a novel therapeutic agent.
Additional information is available at www.alphacorepharma.com
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