– New Pre-Clinical Results Demonstrate that ALN-PCSsc Achieves up to 90% PCSK9 Knockdown and up to 68% Lowering of LDLc in Absence of Statins –
– Pre-clinical Durability Data Support Every-Two-Weeks Dosing –
NEW YORK, NY, USA I October 9, 2013 I The Medicines Company (MDCO) a leading acute/intensive hospital care company, and Alnylam Pharmaceuticals, Inc. (ALNY), a leading RNAi therapeutics company, announced today that their strategic alliance has yielded a lead Development Candidate that is a subcutaneously administered RNAi therapeutic (ALN-PCSsc) targeting PCSK9 for the potential treatment of hypercholesterolemia.
New data from non-human primate studies were presented at the Oligonucleotide Therapeutics Society (OTS) meeting, and show that ALN-PCSsc leads to an up to a 90% PCSK9 knockdown and an up to 68% lowering of LDL cholesterol in the absence of statins. PCSK9 is a protein that regulates low-density lipoprotein (LDL) receptor levels on hepatocytes.
The ALN-PCSsc lead Development Candidate utilizes Alnylam’s GalNAc-siRNA conjugate delivery technology that enables subcutaneous dose administration. Pre-clinical durability data support the potential for every-two-weeks dosing, with possible every-four-weeks dosing.
Additional details of the subcutaneously administered development candidate, and the data, will be presented by John Maraganore, PhD, Chief Executive Officer of Alnylam at The Medicines Company’s Investor & Analyst Day in New York (webcast 8:30ET to noon at www.themedicinescompany.com).
Dr. Maraganore said, “We have rapidly advanced the ALN-PCS collaboration to reach our first goal, which was to designate our Development Candidate by the end of this year. We anticipate submitting an investigative new drug application for ALN-PCSsc with the US Food and Drug Administration in late 2014. This is an important program within our ‘Alnylam 5×15’ product development and commercialization strategy focused on RNAi therapeutics directed toward genetically validated targets.”
“These new data with subcutaneous delivery support our belief that the unique mechanism of action for ALN-PCS holds great promise for a differentiated and potentially best-in-class strategy for PCSK9 antagonism,” said Clive Meanwell, MD, PhD, Chairman and Chief Executive Officer of The Medicines Company. “Subcutaneous dosing holds the potential for administration of a therapeutic in patients less frequently and less invasively than intravenous dosing.”
The Medicines Company-Alnylam PCSK9 collaboration plan is for Alnylam to complete certain pre-clinical and additional Phase I clinical studies. The Medicines Company is responsible for leading and funding development from Phase II forward and commercializing the ALN-PCS program, if successful.
Last week, The Lancet published results from a Phase I trial with ALN-PCS02, a systemically administered RNAi therapeutic. The data presented today are for the subcutaneous form ALN-PCSsc.
About PCSK9
PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein that regulates low-density lipoprotein (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-C.
About Hypercholesterolemia
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-C goals with statin therapy, including genetic 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.
About ALN-PCS
ALN-PCS is an investigational, 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 low-density lipoprotein cholesterol (LDL-C, or “bad” cholesterol). ALN-PCS therapies are PCSK9 synthesis inhibitors that lower 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). PCSK9 synthesis inhibition through an RNAi mechanism has the potential to lower tissue and circulating plasma PCSK9 protein levels resulting in higher LDL receptor levels in the liver, and subsequently lower LDL-C levels in the blood stream. Lower LDL-C is associated with a decreased risk of cardiovascular disease, including myocardial infarction and stroke.
About GalNAc Conjugates
GalNAc-siRNA conjugates are a proprietary Alnylam delivery platform and are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor. Research findings demonstrate potent and durable target gene silencing, as well as a wide therapeutic index, with subcutaneously administered GalNAc-siRNAs from multiple “Alnylam 5×15” programs.
About RNA Interference (RNAi)
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
About The Medicines Company
The Medicines Company’s purpose is to save lives, alleviate suffering and contribute to the economics of healthcare by focusing on 3000 leading acute/intensive care hospitals worldwide. Its vision is to be a leading provider of solutions in three areas: acute cardiovascular care, surgery and perioperative care, and serious infectious disease care. The company operates in the Americas, Europe and the Middle East, and Asia Pacific regions with global centers today in Parsippany, NJ, USA and Zurich, Switzerland.
SOURCE: The Medicines Company
Post Views: 170
– New Pre-Clinical Results Demonstrate that ALN-PCSsc Achieves up to 90% PCSK9 Knockdown and up to 68% Lowering of LDLc in Absence of Statins –
– Pre-clinical Durability Data Support Every-Two-Weeks Dosing –
NEW YORK, NY, USA I October 9, 2013 I The Medicines Company (MDCO) a leading acute/intensive hospital care company, and Alnylam Pharmaceuticals, Inc. (ALNY), a leading RNAi therapeutics company, announced today that their strategic alliance has yielded a lead Development Candidate that is a subcutaneously administered RNAi therapeutic (ALN-PCSsc) targeting PCSK9 for the potential treatment of hypercholesterolemia.
New data from non-human primate studies were presented at the Oligonucleotide Therapeutics Society (OTS) meeting, and show that ALN-PCSsc leads to an up to a 90% PCSK9 knockdown and an up to 68% lowering of LDL cholesterol in the absence of statins. PCSK9 is a protein that regulates low-density lipoprotein (LDL) receptor levels on hepatocytes.
The ALN-PCSsc lead Development Candidate utilizes Alnylam’s GalNAc-siRNA conjugate delivery technology that enables subcutaneous dose administration. Pre-clinical durability data support the potential for every-two-weeks dosing, with possible every-four-weeks dosing.
Additional details of the subcutaneously administered development candidate, and the data, will be presented by John Maraganore, PhD, Chief Executive Officer of Alnylam at The Medicines Company’s Investor & Analyst Day in New York (webcast 8:30ET to noon at www.themedicinescompany.com).
Dr. Maraganore said, “We have rapidly advanced the ALN-PCS collaboration to reach our first goal, which was to designate our Development Candidate by the end of this year. We anticipate submitting an investigative new drug application for ALN-PCSsc with the US Food and Drug Administration in late 2014. This is an important program within our ‘Alnylam 5×15’ product development and commercialization strategy focused on RNAi therapeutics directed toward genetically validated targets.”
“These new data with subcutaneous delivery support our belief that the unique mechanism of action for ALN-PCS holds great promise for a differentiated and potentially best-in-class strategy for PCSK9 antagonism,” said Clive Meanwell, MD, PhD, Chairman and Chief Executive Officer of The Medicines Company. “Subcutaneous dosing holds the potential for administration of a therapeutic in patients less frequently and less invasively than intravenous dosing.”
The Medicines Company-Alnylam PCSK9 collaboration plan is for Alnylam to complete certain pre-clinical and additional Phase I clinical studies. The Medicines Company is responsible for leading and funding development from Phase II forward and commercializing the ALN-PCS program, if successful.
Last week, The Lancet published results from a Phase I trial with ALN-PCS02, a systemically administered RNAi therapeutic. The data presented today are for the subcutaneous form ALN-PCSsc.
About PCSK9
PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein that regulates low-density lipoprotein (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-C.
About Hypercholesterolemia
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-C goals with statin therapy, including genetic 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.
About ALN-PCS
ALN-PCS is an investigational, 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 low-density lipoprotein cholesterol (LDL-C, or “bad” cholesterol). ALN-PCS therapies are PCSK9 synthesis inhibitors that lower 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). PCSK9 synthesis inhibition through an RNAi mechanism has the potential to lower tissue and circulating plasma PCSK9 protein levels resulting in higher LDL receptor levels in the liver, and subsequently lower LDL-C levels in the blood stream. Lower LDL-C is associated with a decreased risk of cardiovascular disease, including myocardial infarction and stroke.
About GalNAc Conjugates
GalNAc-siRNA conjugates are a proprietary Alnylam delivery platform and are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor. Research findings demonstrate potent and durable target gene silencing, as well as a wide therapeutic index, with subcutaneously administered GalNAc-siRNAs from multiple “Alnylam 5×15” programs.
About RNA Interference (RNAi)
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
About The Medicines Company
The Medicines Company’s purpose is to save lives, alleviate suffering and contribute to the economics of healthcare by focusing on 3000 leading acute/intensive care hospitals worldwide. Its vision is to be a leading provider of solutions in three areas: acute cardiovascular care, surgery and perioperative care, and serious infectious disease care. The company operates in the Americas, Europe and the Middle East, and Asia Pacific regions with global centers today in Parsippany, NJ, USA and Zurich, Switzerland.
SOURCE: The Medicines Company
Post Views: 170
