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https://www.readbyqxmd.com/read/26109850/profile-of-evolocumab-and-its-potential-in-the-treatment-of-hyperlipidemia
#1
REVIEW
Arrigo F G Cicero, Alessandro Colletti, Claudio Borghi
Despite the proven efficacy of statins, they often fail to achieve low-density lipoprotein (LDL) cholesterol goals, especially in high-risk patients. Moreover, a large number of subjects cannot tolerate statins or full doses of these drugs, in particular patients with familial hypercholesterolemia. Thus, there is a need for additional effective LDL cholesterol-reducing agents. Evolocumab (AMG145) is a monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 that binds to the liver LDL receptor and prevents it from normal recycling by targeting it for degradation...
2015: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/25491324/proprotein-convertase-subtilisin-kexin-9-inhibitors-next-generation-in-lipid-lowering-therapy
#2
REVIEW
Haralampos Milionis, George Liamis, Moses Elisaf
INTRODUCTION: Statins reduce low-density lipoprotein cholesterol (LDL-C) and are currently the mainstay in the treatment of hyperlipidaemia and subsequently the prevention of atherosclerotic cardiovascular disease (CVD). Nevertheless, there is a need to further lower LDL-C, especially in subjects with severe forms of hypercholesterolaemia despite maximum doses of conventional drugs and/or in those intolerant to existing therapies. AREAS COVERED: Emerging therapeutic approaches to lowering LDL-C involve blocking LDL-receptor degradation by serum proprotein convertase subtilisin kexin 9 (PCSK9)...
February 2015: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/24993279/pcsk9-and-ldlr-the-yin-yang-in-the-cellular-uptake-of-cholesterol
#3
E Morales-Villegas
The intracellular concentration of cholesterol is a vital constant influenced by the uptake, metabolism and excretion of cholesterol. The synthesis and expression of the PCSK9-LDLR duo is one of the most important mechanisms to regulate this constant; in a physiological state, the yin-yang balance between PCSK9 and LDLR regulates the entry of cholesterol into the cell to keep the intracellular cholesterol concentration stable. The mapping of the human gene encoding the serine protease PCSK9, located at 1p32-3, has allowed the identification of mutations with "gain" and "loss" of protease functions...
July 1, 2014: Current Hypertension Reviews
https://www.readbyqxmd.com/read/24661068/efficacy-and-safety-profile-of-evolocumab-amg145-an-injectable-inhibitor-of-the-proprotein-convertase-subtilisin-kexin-type-9-the-available-clinical-evidence
#4
REVIEW
Arrigo F G Cicero, Elisa Tartagni, Sibel Ertek
INTRODUCTION: Despite the proven efficacy of statins, they are often reported to be inadequate to achieve low-density lipoprotein cholesterol (LDL-C) goals (especially in high-risk patients). Moreover, a large number of subjects cannot tolerate statins or full doses of these drugs. Thus, there is a need for additional effective LDL-C reducing agents. AREAS COVERED: Evolocumab (AMG145) is a monoclonal antibody inhibiting the proprotein convertase subtilisin/kexin type 9 that binds to the liver LDL receptor and prevents it from normal recycling by targeting it for degradation...
June 2014: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/24407047/antihyperlipidemic-therapies-targeting-pcsk9
#5
REVIEW
Michael Weinreich, William H Frishman
Hyperlipidemia is a major cause of cardiovascular disease despite the availability of first-line cholesterol-lowering agents such as statins. A new therapeutic approach to lowering low-density lipoprotein-cholesterol (LDL-C) acts by blocking LDL-receptor degradation by serum proprotein convertase subtilisin kexin 9 (PCSK9). Human monoclonal antibodies that target PCSK9 and its interaction with the LDL receptor are now in clinical trials (REGN727/SAR23653, AMG145, and RN316). These agents are administered by either subcutaneous or intravenous routes, and have been shown to have major LDL-C and apolipoprotein B effects when combined with statins...
May 2014: Cardiology in Review
https://www.readbyqxmd.com/read/24354905/an-update-on-the-clinical-development-of-proprotein-convertase-subtilisin-kexin-9-inhibitors-novel-therapeutic-agents-for-lowering-low-density-lipoprotein-cholesterol
#6
REVIEW
Hua Ling, Tammy L Burns, Daniel E Hilleman
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an essential role in the degradation of low-density lipoprotein C (LDL-C) receptors, and PCSK9 inhibitors have recently emerged as a potential treatment option to reduce LDL-C. Our paper reviewed the current available Phase II clinical trials of PCSK9 inhibitors for the treatment of dyslipidemia. A second objective of this review was to evaluate the potential clinical role of PCSK9 inhibitors in the management of dyslipidemia. Studies evaluating the efficacy and safety of any PCSK9 inhibitors in patients with dyslipidemia were included...
April 2014: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/24259646/biologics-for-the-treatment-of-dyslipidemias-a-look-beyond-conventional-therapy
#7
REVIEW
Connie H Yoon, Kristin Watson
OBJECTIVE: To evaluate the monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) in the management of dyslipidemias. DATA SOURCES: MEDLINE/PubMed, NHS Evidence, TRIP database and EMBASE searches were conducted using the terms proprotein convertase subtilisin/kexin type 9, PCSK9, and monoclonal antibody. No date limits were utilized; search results were current to September 2013. STUDY SELECTION AND DATA EXTRACTION: Articles were limited to phase 2 or 3 clinical trials of monoclonal antibodies to PCSK9 assessing surrogate markers of clinical end points...
February 2014: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/23884353/amg145-a-monoclonal-antibody-against-proprotein-convertase-subtilisin-kexin-type-9-significantly-reduces-lipoprotein-a-in-hypercholesterolemic-patients-receiving-statin-therapy-an-analysis-from-the-ldl-c-assessment-with-proprotein-convertase-subtilisin-kexin
#8
RANDOMIZED CONTROLLED TRIAL
Nihar R Desai, Payal Kohli, Robert P Giugliano, Michelle L O'Donoghue, Ransi Somaratne, Jing Zhou, Elaine B Hoffman, Fannie Huang, William J Rogers, Scott M Wasserman, Robert Scott, Marc S Sabatine
BACKGROUND: Lipoprotein(a) [Lp(a)] is an emerging risk factor for cardiovascular disease. Currently, there are few available therapies to lower Lp(a). We sought to evaluate the impact of AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), on Lp(a). METHODS AND RESULTS: As part of the LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial, 631 patients with hypercholesterolemia receiving statin therapy were randomized to receive AMG145 at 1 of 3 different doses every 2 weeks or 1 of 3 different doses every 4 weeks versus placebo...
August 27, 2013: Circulation
https://www.readbyqxmd.com/read/23652470/pcsk9-inhibitors
#9
REVIEW
Michel Farnier
PURPOSE OF REVIEW: To summarize the therapeutic strategies to inhibit PCSK9 and to describe the main results obtained in phase I and II trials with monoclonal antibodies targeting PCSK9. RECENT FINDINGS: Among the various approaches for PCSK9 inhibition, human data are only available for inhibition of PCSK9 binding to LDL receptor by monoclonal antibodies. Promising preclinical studies have also been reported with other strategies, including inhibition of PCSK9 synthesis by gene silencing agents...
June 2013: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/23128163/effect-of-a-monoclonal-antibody-to-pcsk9-on-low-density-lipoprotein-cholesterol-levels-in-statin-intolerant-patients-the-gauss-randomized-trial
#10
RANDOMIZED CONTROLLED TRIAL
David Sullivan, Anders G Olsson, Rob Scott, Jae B Kim, Allen Xue, Val Gebski, Scott M Wasserman, Evan A Stein
CONTEXT: An estimated 10% to 20% of patients cannot tolerate statins or adequate doses to achieve treatment goals. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, promoting their degradation and increasing LDL cholesterol levels. In phase 1 studies, a human monoclonal antibody to PCSK9, AMG145, was well tolerated and reduced LDL cholesterol levels. OBJECTIVE: To assess the efficacy and tolerability of AMG145 in patients with statin intolerance due to muscle-related side effects...
December 19, 2012: JAMA: the Journal of the American Medical Association
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