Cited by 665Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismLipid metabolism and disorders

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Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol

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Stein, Evan A., Mellis, Scott, Yancopoulos, George D., Stahl, Neil, Logan, Douglas, Smith, William B., Lisbon, Eleanor, Gutierrez, Maria, Webb, Cheryle, Wu, Richard, Du, Yunling, Kranz, Therese, Gasparino, Evelyn, Swergold, Gary D.·2012·New England Journal of Medicine

DOI 10.1056/nejmoa1105803

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Abstract

BACKGROUND: Proprotein convertase subtilisin/kexin 9 (PCSK9), one of the serine proteases, binds to low-density lipoprotein (LDL) receptors, leading to their accelerated degradation and to increased LDL cholesterol levels. We report three phase 1 studies of a monoclonal antibody to PCSK9 designated as REGN727/SAR236553 (REGN727). METHODS: In healthy volunteers, we performed two randomized, single ascending-dose studies of REGN727 administered either intravenously (40 subjects) or subcutaneously (32 subjects), as compared with placebo. These studies were followed by a randomized, placebo-controlled, multiple-dose trial in adults with heterozygous familial hypercholesterolemia who were receiving atorvastatin (21 subjects) and those with nonfamilial hypercholesterolemia who were receiving treatment with atorvastatin (30 subjects) (baseline LDL cholesterol, >100 mg per deciliter [2.6 mmol per liter]) or a modified diet alone (10 subjects) (baseline LDL cholesterol, >130 mg per deciliter [3.4 mmol per liter]). REGN727 doses of 50, 100, or 150 mg were administered subcutaneously on days 1, 29, and 43. The primary outcome for all studies was the occurrence of adverse events. The principal secondary outcome was the effect of REGN727 on the lipid profile. RESULTS: Among subjects receiving REGN727, there were no discontinuations because of adverse events. REGN727 significantly lowered LDL cholesterol levels in all the studies. In the multiple-dose study, REGN727 doses of 50, 100, and 150 mg reduced measured LDL cholesterol levels in the combined atorvastatin-treated populations to 77.5 mg per deciliter (2.00 mmol per liter), 61.3 mg per deciliter (1.59 mmol per liter), and 53.8 mg per deciliter (1.39 mmol per liter), for a difference in the change from baseline of -39.2, -53.7, and -61.0 percentage points, respectively, as compared with placebo (P<0.001 for all comparisons). CONCLUSIONS: In three phase 1 trials, a monoclonal antibody to PCSK9 significantly reduced LDL cholesterol levels in healthy volunteers and in subjects with familial or nonfamilial hypercholesterolemia. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT01026597, NCT01074372, and NCT01161082.).

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Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease
Cohen, J. C., Boerwinkle, E., Mosley, T. H., & Hobbs, H. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054013 · Cited by 3,181
Mutations in PCSK9 cause autosomal dominant hypercholesterolemia
Abifadel, M., Varret, M., Rabès, J.-P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., et al. (2003) · Nature Genetics · doi:10.1038/ng1161 · Cited by 2,985
Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9
Cohen, J., Pertsemlidis, A., Kotowski, I. K., Graham, R., Garcia, C. K., & Hobbs, H. H. (2005) · Nature Genetics · doi:10.1038/ng1509 · Cited by 1,381
Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and inlivers of parabiotic mice
Lagace, T. A., Curtis, D. E., Garuti, R., McNutt, M. C., Park, S. W., Prather, H. B., Anderson, N. N., Ho, Y. K., Hammer, R. E., & Horton, J. D. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29383 · Cited by 681
Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9
Rashid, S., Curtis, D. E., Garuti, R., Anderson, N. N., Bashmakov, Y., Ho, Y. K., Hammer, R. E., Moon, Y.-A., & Horton, J. D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501652102 · Cited by 679
Molecular Characterization of Loss-of-Function Mutations in PCSK9 and Identification of a Compound Heterozygote
Zhao, Z., Tuakli-Wosornu, Y., Lagace, T. A., Kinch, L. N., Grishin, N. V., Horton, J. D., Cohen, J. C., & Hobbs, H. H. (2006) · The American Journal of Human Genetics · doi:10.1086/507488 · Cited by 642
Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype
Maxwell, K. N., & Breslow, J. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402133101 · Cited by 613
A Spectrum of PCSK9 Alleles Contributes to Plasma Levels of Low-Density Lipoprotein Cholesterol
Kotowski, I. K., Pertsemlidis, A., Luke, A., Cooper, R. S., Vega, G. L., Cohen, J. C., & Hobbs, H. H. (2006) · The American Journal of Human Genetics · doi:10.1086/500615 · Cited by 517
Post-transcriptional Regulation of Low Density Lipoprotein Receptor Protein by Proprotein Convertase Subtilisin/Kexin Type 9a in Mouse Liver
Park, S. W., Moon, Y.-A., & Horton, J. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410077200 · Cited by 452
A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates
Chan, J. C. Y., Piper, D. E., Cao, Q., Liu, D., King, C., Wang, W., Tang, J., Liu, Q., Higbee, J., Xia, Z., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903849106 · Cited by 371

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Bergeron, N., Phan, B. A. P., Ding, Y., Fong, A., & Krauss, R. M. (2015) · Circulation · doi:10.1161/circulationaha.115.016080 · Cited by 171
Induction of Sustained Hypercholesterolemia by Single Adeno-Associated Virus–Mediated Gene Transfer of Mutant hPCSK9
Roche-Molina, M., Sanz‐Rosa, D., Cruz, F. M., García‐Prieto, J., López, S., Abia, R., Muriana, F. J. G., Fuster, V., Ibáñez, B., & Bernal, J. A. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303617 · Cited by 191
Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation
Kosenko, T., Golder, M., Leblond, G., Weng, W., & Lagace, T. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.421370 · Cited by 181
New LDL-Cholesterol Lowering Therapies: Pharmacology, Clinical Trials, and Relevance to Acute Coronary Syndromes
Sahebkar, A., & Watts, G. F. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.06.019 · Cited by 181
The Severe Hypercholesterolemia Phenotype
Sniderman, A. D., Tsimikas, S., & Fazio, S. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.01.060 · Cited by 180
New Therapies Targeting apoB Metabolism for High-Risk Patients with Inherited Dyslipidaemias: What Can the Clinician Expect?
Sahebkar, A., & Watts, G. F. (2013) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-013-6479-4 · Cited by 176
The hypercholesterolemia-risk gene SORT1 facilitates PCSK9 secretion
Gustafsen, C., Kjolby, M., Nyegaard, M., Mattheisen, M., Lundhede, J., Buttenschøn, H., Mors, O., Bentzon, J. F., Madsen, P., Nykjaer, A., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.006 · Cited by 170
Dyslipidemia
Arvanitis, M., & Lowenstein, C. J. (2023) · Annals of Internal Medicine · doi:10.7326/aitc202306200 · Cited by 174
Statins and PCSK9 inhibitors: A new lipid-lowering therapy
Gallego-Colon, E., Daum, A., & Yosefy, C. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173114 · Cited by 156
Integrated guidance on the care of familial hypercholesterolemia from the International FH Foundation
Watts, G. F., Gidding, S. S., Wierzbicki, A. S., Toth, P. P., Rodrigo Alonso, K., Brown, W. V., Bruckert, É., Defesche, J. C., Lin, K. K., Livingston, M., et al. (2014) · Journal of clinical lipidology · doi:10.1016/j.jacl.2014.01.002 · Cited by 165
A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption
Zhang, Y., Fu, Z.-Y., Wei, J. N., Qi, W., Baituola, G., Luo, J., Meng, Y. J., Guo, S., Yin, H., Jiang, S., et al. (2018) · Science · doi:10.1126/science.aao6575 · Cited by 163
Identification of a Small Peptide That Inhibits PCSK9 Protein Binding to the Low Density Lipoprotein Receptor
Zhang, Y., Eigenbrot, C. W., Zhou, L., Shia, S., Li, W., Quan, C. L., Tom, J., Moran, P., Lello, P. D., Skelton, N. J., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.514067 · Cited by 161
Targeting PCSK9 to tackle cardiovascular disease
Hummelgaard, S., Vilstrup, J. P., Gustafsen, C., Glerup, S., & Weyer, K. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108480 · Cited by 150
Recent Advances in Treatment of Coronary Artery Disease: Role of Science and Technology
Kandaswamy, E., & Zuo, L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020424 · Cited by 164
The safety of therapeutic monoclonal antibodies: Implications for cardiovascular disease and targeting the PCSK9 pathway
Catapano, A. L., & Papadopoulos, N. J. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.01.044 · Cited by 158
Increased Plasma PCSK9 Levels Are Associated with Reduced Endotoxin Clearance and the Development of Acute Organ Failures during Sepsis
Boyd, J. H., Fjell, C. D., Russell, J. A., Sirounis, D., Cirstea, M. S., & Walley, K. R. (2016) · Journal of Innate Immunity · doi:10.1159/000442976 · Cited by 157
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Steg, P. G., Szarek, M. J., Bhatt, D. L., Bittner, V., Brégeault, M.-F., Dalby, A. J., Díaz, R., Edelberg, J. M., Goodman, S. G., Hanotin, C., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.038840 · Cited by 153
Advances in lipid-lowering therapy through gene-silencing technologies
Nordestgaard, B. G., Nicholls, S. J., Langsted, A., Ray, K. K., & Tybjærg‐Hansen, A. (2018) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2018.3 · Cited by 148
Inhibiting PCSK9 — biology beyond LDL control
Stoekenbroek, R. M., Lambert, G., Cariou, B., & Hovingh, G. K. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0110-5 · Cited by 141
Genetics of Coronary Artery Disease
Roberts, R. (2014) · Circulation Research · doi:10.1161/circresaha.114.302692 · Cited by 144
Peptide-Based Anti-PCSK9 Vaccines - An Approach for Long-Term LDLc Management
Galabova, G., Brunner, S., Winsauer, G., Juno, C., Wanko, B., Mairhofer, A., Lührs, P., Schneeberger, A., von Bonin, A., Mattner, F., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114469 · Cited by 141
Dual TLR agonist nanodiscs as a strong adjuvant system for vaccines and immunotherapy
Kuai, R., Sun, X., Yuan, W., Ochyl, L. J., Xu, Y., Najafabadi, A. H., Scheetz, L. M., Yu, M., Balwani, I., Schwendeman, A. A., et al. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.04.041 · Cited by 138
Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9)
Schulz, R., Schlüter, K.-D., & Laufs, U. (2015) · Basic Research in Cardiology · doi:10.1007/s00395-015-0463-z · Cited by 137
Pharmacologic Profile of the Adnectin BMS-962476, a Small Protein Biologic Alternative to PCSK9 Antibodies for Low-Density Lipoprotein Lowering
Mitchell, T. S., Chao, G., Sitkoff, D. F., Lo, F., Monshizadegan, H., Meyers, D. S., Low, S., Russo, K., DiBella, R. A., Denhez, F., et al. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.214221 · Cited by 140
Elevated PCSK9 Levels in Untreated Patients With Heterozygous or Homozygous Familial Hypercholesterolemia and the Response to High‐Dose Statin Therapy
Raal, F. J., Panz, V. R., Immelman, A., & Pilcher, G. J. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.112.000028 · Cited by 135
Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled analysis of 1359 patients in four phase 2 trials
Stein, E. A., Giugliano, R. P., Koren, M. J., Raal, F. J., Roth, E. M., Weiss, R., Sullivan, D., Wasserman, S. M., Somaratne, R., Kim, J. B., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu085 · Cited by 130
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Roth, E. M., Moriarty, P. M., Bergeron, J., Langslet, G., Manvelian, G. Z., Zhao, J. M., Baccara‐Dinet, M. T., & Rader, D. J. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.08.043 · Cited by 128
Familial Hypercholesterolemia
Bouhairie, V. E., & Goldberg, A. C. (2015) · Cardiology Clinics · doi:10.1016/j.ccl.2015.01.001 · Cited by 146
Targeting PCSK9 for hypercholesterolemia
Norata, G. D., Tibolla, G., & Catapano, A. L. (2014) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-140025 · Cited by 127
PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease
Schmidt, A. F., Carter, J.-P. L., Pearce, L. S., Wilkins, J. T., Overington, J. P., Hingorani, A. D., & Casas, J. (2020) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011748.pub3 · Cited by 123
Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation
Seidah, N. G., Poirier, S., Denis, M., Parker, R., Miao, B., Mapelli, C., Prat, A., Wassef, H., Davignon, J., Hajjar, K. A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041865 · Cited by 117
Glucose-Sensitive Myokine/Cardiokine MG53 Regulates Systemic Insulin Response and Metabolic Homeostasis
Wu, H., Zhang, Y., Cao, C., Hu, X., Fang, M., Yao, Y., Li, J., Chen, G., Jiang, P., Zhang, S., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.037216 · Cited by 121
Inclisiran—New hope in the management of lipid disorders?
Dyrbuś, K., Gąsior, M., Penson, P., Ray, K. K., & Banach, M. (2020) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2019.11.001 · Cited by 120
Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody
Hopkins, P. N., Defesche, J. C., Fouchier, S. W., Bruckert, É., Luc, G., Cariou, B., Sjouke, B., Leren, T. P., Harada‐Shiba, M., Mabuchi, H., et al. (2015) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.115.001129 · Cited by 116
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PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors: past, present, and the future
Shimada, Y. J., & Cannon, C. P. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv174 · Cited by 98
Plasma proprotein convertase subtilisin/kexin type 9 levels and the risk of first cardiovascular events
Ridker, P. M., Rifai, N., Bradwin, G., & Rose, L. M. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv568 · Cited by 113
Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
de Vries, P. S., Brown, M. R., Bentley, A. R., Sung, Y. J., Winkler, T. W., Ντάλλα, Ι., Schwander, K., Kraja, A. T., Guo, X., Franceschini, N., et al. (2019) · American Journal of Epidemiology · doi:10.1093/aje/kwz005 · Cited by 113
Plasma PCSK9 Levels Are Elevated with Acute Myocardial Infarction in Two Independent Retrospective Angiographic Studies
Almontashiri, N. A. M., Vilmundarson, R. O., Ghasemzadeh, N., Dandona, S., Roberts, R., Quyyumi, A. A., Chen, H., & Stewart, A. F. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106294 · Cited by 109
Risk prediction with proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with stable coronary disease on statin treatment
Werner, C. M., Hoffmann, M. M., Winkler, K., Böhm, M., & Laufs, U. (2014) · Vascular Pharmacology · doi:10.1016/j.vph.2014.03.004 · Cited by 109

Authors: Stein, E. A., Mellis, S., Yancopoulos, G. D., Stahl, N., Logan, D., Smith, W. B., Lisbon, E., Gutierrez, M., Webb, C., Wu, R., Du, Y., Kranz, T., Gasparino, E., & Swergold, G. D.
Affiliations: Regeneron (United States) (US)
Medpace (United States) (US)
University of Tennessee Medical Center (US)
IQVIA (United States) (US)
ORCID: Stein, Evan A.
Mellis, Scott
Stahl, Neil
Lisbon, Eleanor
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2012-03-22
Volume: 366
Issue: 12
Pages: 1108-1118
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1105803
OpenAlex: W1989730880
Semantic Scholar: 04c1ea8c55c4bae0da3106e47141bac81e1bb585
Cited by: 664
References: 15
Citations by year: 2026: 12 · 2025: 11 · 2024: 29 · 2023: 22 · 2022: 19 · 2021: 20 · 2020: 38 · 2019: 29 · 2018: 46 · 2017: 58 · 2016: 62 · 2015: 86 · 2014: 83 · 2013: 92 · 2012: 57
FWCI: 103.85
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: Sanofi
Regeneron Pharmaceuticals
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: PCSK9, monoclonal antibodies, LDL cholesterol, LDL receptor degradation, hypercholesterolemia, familial hypercholesterolemia, atorvastatin, lipid profile, adverse events, dose escalation, cholesterol absorption inhibition
MeSH terms: Atorvastatin, Proprotein Convertase 9, Adult, Antibodies, Monoclonal, Anticholesteremic Agents, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Heptanoic Acids, Humans, Hypercholesterolemia, Hyperlipoproteinemia Type II, Injections, Intravenous, Injections, Subcutaneous, Lipoproteins, Cholesterol, LDL, Male, Middle Aged, Pyrroles, Receptors, LDL, Serine Endopeptidases, Least-Squares Analysis, Proprotein Convertases, Antibodies, Monoclonal, Humanized

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Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol

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