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El ácido bempedoico demuestra beneficios en hipercolesterolemia en nuevos ensayos clínicos presentados en la 69 Sesión Científica Anual del Colegio Americano de Cardiología y el Congreso Mundial de Cardiología (ACC.20/WCC)

Datos presentados en el congreso virtual ACC.20/WCC

  • El ácido bempedoico se está desarrollando como un tratamiento oral, primero en su clase y asequible para reducir el colesterol  unido a  lipoproteínas de baja densidad (c-LDL) y que puede combinarse con otros tratamientos orales para reducir el colesterol aún más[1],[2],[3],[4],[5]
  • Los resultados de un estudio fase 2 demuestran una reducción del 40% del colesterol LDL-c en pacientes con diabetes tipo 2 y alto riesgo de eventos cardiovasculares[6]
  • Dos análisis combinados de cuatro ensayos de fase 3 en los que participaron más de 3.600 pacientes mostraron que el ácido bempedoico reduce significativamente la proteína C reactiva de alta sensibilidad y el LDL-c[7],[8]

Madrid, 13 de abril de 2020. – Daiichi Sankyo Europa ha anunciado los resultados de dos análisis combinados de cuatro estudios clínicos de fase 3 del ácido bempedoico y, por otra parte, las conclusiones de un estudio de fase 2 del comprimido combinado a dosis fija de ácido bempedoico / ezetimiba, que demuestran un beneficio en la hipercolesterolemia. Los datos se han presentado en la edición virtual de la 69 Sesión Científica del Colegio Americano de Cardiología y el Congreso Mundial de Cardiología (ACC.20/WCC).

El estudio 058 es un estudio de fase 2, con una duración de 12 semanas, para el comprimido combinado a dosis fija de ácido bempedoico /ezetimiba con pacientes adultos con diabetes mellitus tipo 2 y alto riesgo de enfermedad cardiovascular.6El comprimido combinado a dosis fija de ácido bempedoico / ezetimiba redujo el c-LDL en un 40% en comparación con el placebo sin aumentar la hemoglobina glicosilada (HbA1c), ni incidir de forma negativa en el control glucémico.6 El comprimido combinado a dosis fija de ácido bempedoico / ezetimiba fue bien tolerado en el estudio 058, y las tasas de incidencia de eventos adversos fueron comparables a las del placebo.6

El primer análisis combinado de cuatro ensayos clínicos de fase 3 que investigaban el ácido bempedoico en pacientes adultos con hipercolesterolemia demostró que el ácido bempedoico producía una reducción significativa del c-LDL, además de otras medidas de lípidos (colesterol total, colesterol unido a lipoproteínas de no alta densidad (no HDL-C), apoproteína B, HDL-C), independientemente del tratamiento de fondo con ezetimiba.7 El uso de ácido bempedoico con o sin terapia de fondo con ezetimiba,  mantuvo el mismo rango de incidencia general de efectos adversos en ambos brazos del estudio.7

El segundo análisis combinado demuestra que el ácido bempedoico reduce la proteína C reactiva de alta sensibilidad (PCRhs), un marcador clave de la inflamación asociado con la enfermedad cardiovascular, en un 42% a las 12 semanas en pacientes con hipercolesterolemia, independientemente de la presencia o la intensidad de la terapia de base con estatinas.8

“Nos alientan todos los datos presentados que demuestran el beneficio potencial del ácido bempedoico para los pacientes adultos que necesitan disminuir sus niveles de c-LDL para reducir el riesgo de sufrir un evento cardiovascular como un infarto agudo de miocardio o un ictus”, indica el doctor Wolfgang Zierhut,jefe del Departamento Médico de Antitrombóticos y Cardiovasculares en DaiichiSankyo Europa. “Es necesario bajar los niveles de c-LDL, tal como indican las últimas guías ESC/EAS, Los datos de fase 2 presentados, que muestran el potencial de reducir el c-LDL para los pacientes con un riesgo particularmente alto debido a la diabetes sin afectar el control glucémico, son prometedores, pero necesitaremos la validación a través de estudios más amplios. Se necesitan urgentemente tratamientos adicionales de reducción de lípidos para apoyar a los pacientes, y esperamos poder conseguir que el ácido bempedoico esté disponible en Europa pronto”, finaliza.

Sobre el ácido bempedoico

Con un mecanismo de acción único, el ácido bempedoico se está desarrollando como un tratamiento primero en su clase, oral y asequible para reducir el colesterol y puede combinarse con otros tratamientos orales para reducir el colesterol aún más.1,2,3,4  El ácido bempedoico inhibe la ATP –citrato liasa (ACL), una enzima que está encargada de la producción de colesterol en el hígado.1,2,3,4

El ácido bempedoico ha recibido la opinión positiva del CHMP para el uso en adultos con hipercolesterolemia primaria (familiar heterocigota  y no familiar) o dislipemia mixta, como complemento a la dieta:1,2,3,4

  • en combinación con estatinas o estatinas y otra terapia de reducción de lípidos en pacientes que no alcancen c-LDL a la dosis máxima de estatinas tolerada o
  • sola o en combinación con otra terapia de reducción de lípidos en pacientes intolerantes a las estatinas o para los que las estatinas están contraindicadas.

El ácido bempedoico actúa en la conocida vía de síntesis del colesterol, con un mecanismo de acción único que permite una reducción adicional del c-LDL cuando se añade al tratamiento con estatinas.[9] Debido a su novedoso mecanismo de acción, el ácido bempedoico no se activa en el músculo esquelético.9

Sobre el ácido bempedoico / ezetimiba

El ácido bempedoico / ezetimiba se está desarrollando como un tratamiento oral que combina dos formas complementarias de reducir el colesterol en un comprimido de toma única diaria.5 El ácido bempedoico / ezetimiba es un comprimido a dosis fija.5

El ácido bempedoico / ezetimiba ha recibido una opinión positiva del CHMP para el tratamiento en adultos de la hipercolesterolemia primaria (familiar heterocigota o no familiar) o la dislipemia mixta en combinación con la dieta:5

  • en combinación con estatinas en pacientes que no alcanzan los objetivos c-LDL con la dosis maxima de estatinas  tolerada o con estatinas y ezetimiba,
  • sola en pacientes que son intolerantes a las estatinas o para los que las estatinas están contraindicadas y no alcanzan los objetivos de c-LDL solo con ezetimiba,
  • en pacientes que ya han sido tratados con la combinación de ácido bempedoico y ezetimiba en comprimidos separados con o sin tratamiento con estatinas.

DaiichiSankyoEuropa comercializa de forma exclusiva estos productos en el Espacio Económico Europeo y en Suiza en virtud del acuerdo de licencia que tiene con Esperion. A través de la excelencia científica y clínica, y un profundo conocimiento de la biología del colesterol, el experimentado equipo de gestión de lípidos de Esperion se ha comprometido a desarrollar nuevos medicamentos para reducir el c-LDL que tendrán un impacto sustancial en la reducción de las enfermedades cardiovasculares globales, la principal causa de muerte en todo el mundo.

 

Contacto

Sonsoles Dorao                                                                            

Comunicación DaiichiSankyo                                                                                    

673168 886                                                                                            

Carlos Mateos / Guiomar López

COM Salud

912236678/ 675 98 77 23

Referencias

[1]Laufs U, et al. Efficacy and Safety of Bempedoic Acid in Patients with Hypercholesterolemia and Statin Intolerance. J Am         Heart Assoc. 2019;8(7):e011662.

[2] Ray KK, et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med. 2019;380:1022–32.

[3] Goldberg AC, et al. Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease. The CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019;322(18):1780–1788. doi:10.1001/jama.2019.16585.

[4] Ballantyne CM, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis. 2018; 277:195–203.

[5] Ballantyne, CM, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J PrevCardiol. 2019; doi 10.1177/2047487319864671.

[6] Bays, HE, et al. Bempedoic acid 180 mg + ezetimibe 10 mg fixed dose combination drug product vs ezetimibe alone or placebo in patients with type 2 diabetes and hypercholesterolemia. Poster presentation at American College of Cardiology’s 69th Scientific Sessions Together with World Congress of Cardiology virtual experience (ACC.20/WCC). March 2020.

[7]Catapano, AL, et al. Bempedoic acid efficacy and safety in patients at high-risk for CVD treated with or without ezetimibe: pooled analysis of 4 phase 3 clinical trials. Poster presentation at American College of Cardiology’s 69th Scientific Sessions Together with World Congress of Cardiology virtual experience (ACC.20/WCC). March 2020.

[8]Stroes, ESG, et al. Factors influencing bempedoic acid-mediated reductions in high sensitivity c-reative protein: analysis of pooled patient-level data from 4 phase 3 clinical trials. Poster presentation at American College of Cardiology’s 69th Scientific Sessions Together with World Congress of Cardiology virtual experience (ACC.20/WCC). March 2020.

[9]Pinkosky SL, et al. Liver- specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nature Communications. 2016; 7:13457. DOI:10.1038/ncomms13457.