PCSK9 Inhibitors: Lots of Work Done, Lots More to Do
Authors: Michael S. Lauer
Journal: Annals of Internal Medicine (2016)

Editorials3 May 2016PCSK9 Inhibitors: Lots of Work Done, Lots More to DoMichael S. Lauer, MDMichael S. Lauer, MDFrom National Institutes of Health, Bethesda, Maryland.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-0422 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Using publicly available data, Williams and colleagues (1) recently constructed "cure networks" that reflected the complex collaborative networks of thousands of people and places that led to the development of 2 novel, transformative drugs: ipilimumab and ivacaftor. Ipilimumab is the first "immunotherapy" cancer treatment, which stimulates the body's immune system to attack cancerous cells. Ivacaftor corrects the defect resulting from a loss-of-function gene mutation that causes the disease phenotype in a subset of patients with cystic fibrosis. At least 7067 scientists from 5666 institutions worked more than 104 years to create ipilimumab. To develop ivacaftor, at least 2857 scientists from ...References1. Williams RS, Lotia S, Holloway AK, Pico AR. From scientific discovery to cures: bright stars within a galaxy. Cell. 2015;163:21-3. [PMID: 26406364] doi:10.1016/j.cell.2015.09.007 CrossrefMedlineGoogle Scholar2. Navarese EP, Kołodziejczak M, Kereiakes DJ, Tantry US, O'Connor C, Gurbel PA. Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies for acute coronary syndrome. A narrative review. Ann Intern Med. 2016;164:600-7. doi:10.7326/M15-2994 LinkGoogle Scholar3. Cohen JC, Hobbs HH. Genetics. Simple genetics for a complex disease. Science. 2013;340:689-90. [PMID: 23661745] doi:10.1126/science.1239101 CrossrefMedlineGoogle Scholar4. Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154-6. [PMID: 12730697] CrossrefMedlineGoogle Scholar5. Cohen JC, Boerwinkle E, Mosley TH, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354:1264-72. [PMID: 16554528] CrossrefMedlineGoogle Scholar6. Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, et al; Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500-9. [PMID: 25773607] doi:10.1056/NEJMoa1500858 CrossrefMedlineGoogle Scholar7. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al; ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1489-99. [PMID: 25773378] doi:10.1056/NEJMoa1501031 CrossrefMedlineGoogle Scholar8. Everett BM, Smith RJ, Hiatt WR. Reducing LDL with PCSK9 inhibitors—the clinical benefit of lipid drugs. N Engl J Med. 2015;373:1588-91. [PMID: 26444323] doi:10.1056/NEJMp1508120 CrossrefMedlineGoogle Scholar9. Navarese EP, Kołodziejczak M, Schulze V, Gurbel PA, Tantry U, Lin Y, et al. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia. A systematic review and meta-analysis. Ann Intern Med. 2015;163:40-51. [PMID: 25915661]. doi:10.7326/M14-2957 LinkGoogle Scholar10. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al; ILLUMINATE Investigators. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109-22. [PMID: 17984165] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From National Institutes of Health, Bethesda, Maryland.Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0422.Corresponding Author: Michael S. Lauer, MD, Office of Extramural Research, National Institutes of Health, Building 1, 1 Center Drive, Bethesda, MD 20892; e-mail, michael.[email protected]gov.This article was published at www.annals.org on 22 March 2016. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoProprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies for Acute Coronary Syndrome Eliano P. Navarese , Michalina Kołodziejczak , Dean J. Kereiakes , Udaya S. Tantry , Christopher O'Connor , and Paul A. Gurbel Metrics Cited byPCSK9 Inhibitors Show Value for Patients and the US Health Care SystemResearch synergy and drug development: Bright stars in neighboring constellationsPCSK9-related LDL-C value is correlated to Rab5 isoform expression level 3 May 2016Volume 164, Issue 9Page: 624-625KeywordsAcute coronary syndromeCholesterolDrugsFamilial hypercholesterolemiaLow density lipoproteinProteolysisRandomized trialsScientistsStatinsThrombosis ePublished: 22 March 2016 Issue Published: 3 May 2016 PDF downloadLoading ...