Financiado en parte por Amgen, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Gilead Sciences, CSL Behring, Regeneron Pharmaceuticals, REGENXBIO, Medicines Company, Kowa Company, Singulex, Novo Nordisk, HLS Therapeutics, Silence Therapeutics, Esperion Therapeutics, Daiichi Sankyo Europe, The Medicines Company
Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol
Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP, ORION-10 and ORION-11 Investigators
The New England journal of medicine · 1,225 citas
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Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiado por la industria
- Empresa
- Amgen
- Empresa
- Eli Lilly and Company
- Empresa
- Pfizer
- Empresa
- AstraZeneca
- Empresa
- Sanofi
- Empresa
- Gilead Sciences
- Empresa
- CSL Behring
- Empresa
- Regeneron Pharmaceuticals
- Empresa
- REGENXBIO
- Empresa
- Medicines Company
- Empresa
- Kowa Company
- Empresa
- Singulex
- Gobierno
- National Institute for Health and Care Research
- Universidad u hospital
- Imperial College London
- Empresa
- Novo Nordisk
- Empresa
- HLS Therapeutics
- Empresa
- Silence Therapeutics
- Empresa
- Esperion Therapeutics
- Universidad u hospital
- NIHR Imperial Biomedical Research Centre
- Empresa
- Daiichi Sankyo Europe
- Empresa
- The Medicines Company
Según 21 financiadores declarados.
Publicación
- Publicado
- 2020-03-18 · N Engl J Med · vol. 382 · número 16 · págs. 1507–1519
- Editorial
- Massachusetts Medical Society
- Citado
- 1,648 citas · más que el 100% de estudios similares · 165.6× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 19 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Cholesterol and Lipid Metabolism · Lipid metabolism and disorders
- Palabras clave
- inclisiran, PCSK9 inhibition, LDL cholesterol lowering, atherosclerotic cardiovascular disease, statin therapy, injection-site adverse events, hypercholesterolemia, lipid-lowering therapy, adverse events, drug safety and efficacy
- MeSH
- humans, cardiovascular diseases, hypercholesterolemia, rna, small interfering, anticholesteremic agents, hydroxymethylglutaryl-coa reductase inhibitors, liver function tests, injections, subcutaneous, drug administration schedule, risk factors, double-blind method, aged, aged, 80 and over, middle aged, female, male, cholesterol, ldl, coronary artery disease, proprotein convertase 9, pcsk9 inhibitors
11 autores
- Kausik Kumar Ray🇺🇸🇩🇪🇬🇧Mayo Clinic; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Imperial College London; Technical University of Munich
- R. Scott Wright🇺🇸🇩🇪🇬🇧Mayo Clinic; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Imperial College London; Technical University of Munich
- David G. Kallend🇺🇸🇩🇪🇬🇧Mayo Clinic; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Imperial College London; Technical University of Munich
- Wolfgang Köenig🇺🇸🇩🇪🇬🇧Mayo Clinic; Universität Ulm; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Imperial College London; Technical University of Munich
- Lawrence A. Leiter🇨🇦🇺🇸🇩🇪🇬🇧St. Michael's Hospital; Mayo Clinic; University of Toronto; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Imperial College London; Technical University of Munich
- Frederick Johan Raal🇺🇸🇿🇦🇩🇪🇬🇧Mayo Clinic; University of the Witwatersrand; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Imperial College London; Technical University of Munich
- Jenna A. Bisch🇺🇸🇩🇪🇬🇧Mayo Clinic; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Medicines Company (United States); Imperial College London; Technical University of Munich
- Tara Richardson🇺🇸🇩🇪🇬🇧Mayo Clinic; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Medicines Company (United States); Imperial College London; Technical University of Munich
- Mark J Jaros🇺🇸🇩🇪🇬🇧Mayo Clinic; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Imperial College London; Technical University of Munich
- Peter L. J. Wijngaard🇺🇸🇩🇪🇬🇧Mayo Clinic; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Medicines Company (United States); Imperial College London; Technical University of Munich
- John J.P. Kastelein🇺🇸🇳🇱🇩🇪🇬🇧Mayo Clinic; Amsterdam UMC Location University of Amsterdam; German Centre for Cardiovascular Research; Deutsches Herzzentrum München; Imperial College London; Technical University of Munich; University of Amsterdam
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing.
Methods
We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540.
Results
A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (±SD) LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter (2.71±0.99 mmol per liter) and 105.5±39.1 mg per deciliter (2.73±1.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo). Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in the ORION-10 trial and 4.7% vs. 0.5% in the ORION-11 trial); such reactions were generally mild, and none were severe or persistent.
Conclusions
Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo. (Funded by the Medicines Company; ORION-10 and ORION-11 ClinicalTrials.gov numbers, NCT03399370 and NCT03400800.).
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