Noticias

04/10/2017

La EMA valida la solicitud de autorización de Encorafenib y Binimetinib

Los Laboratorios Pierre Fabre, actualmente el 2.º mayor grupo farmacéutico privado francés, han anunciado que la Agencia Europea de Medicamentos (EMA) ha validado las solicitudes de autorización de comercialización (SAC) para el uso de la combinación de 45 mg de Binimetinib dos veces al día y 450 mg de Encorafenib una vez al día (COMBO450) para el tratamiento de pacientes con melanoma irresecable o metastático con mutación de BRAF. Las solicitudes se apoyan en los datos del estudio pivotal de fase 3 COLUMBUS, los cuales mostraron que los pacientes que recibieron la combinación de Binimetinib y Encorafenib tuvieron una supervivencia libre de progresión (SLP) significativamente más larga en comparación con los pacientes que recibieron Vemurafenib.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 

 

" Los resultados de COLUMBUS, incluyendo la supervivencia libre de progresión, la tasa de respuesta objetiva, la intensidad de la dosis y la tolerabilidad de la combinación, ofrecen un contenido sólido y coherente a través de múltiples criterios de evaluación para este estudio". "Nos complace que la EMA haya iniciado la revisión de la SAC de Binimetinib y Encorafenib. Si se aprueba, la combinación desarrollada conjuntamente con Array BioPharma se convertiría en una importante nueva opción para pacientes con melanoma irresecable o metastatico con la mutación de BRAF," afirmó Frédéric Duchesne, Presidente y CEO de Pierre Fabre Pharmaceuticals.

 

Resultados de COLUMBUS

Tal como se presentó en el Congreso Anual de la Sociedad para la Investigación de Melanoma del 2016, los resultados de la Parte 1 del estudio COLUMBUS mostraron que el COMBO450 extiende de forma significativa la SLP en pacientes con melanoma con mutación de BRAF avanzado, con una SLP de 14,9 meses en comparación con los 7,3 meses que se observaron con Vemurafenib, y ofrece una reducción de riesgo significativa del 46 % en la progresión de la enfermedad o muerte [ hazard ratio (HR) 0,54; (IC 95 % 0,41-0,71; P<0,001)]. Como parte del diseño del estudio, el análisis primario se basó en una revisión central independiente ciega (BICR) de imágenes radiológicas del paciente, analizando también los resultados de la revisión local en el centro de investigación.

La combinación de Encorafenib y Binimetinib también demostró una mejora en la tasa de respuesta global confirmada (TRG; respuesta completa más respuesta parcial), versus Vemurafenib (-63% vs 40%).

En este estudio, COMBO450 resultó en general bien tolerado, permitiendo una intensidad de dosis relativa media para Encorafenib y Binimetinib del 100 % y del 99,6 % respectivamente, con un tratamiento o una duración media de 51 semanas. Los efectos indeseables (EI) de grado 3/4 que se produjeron en más del 5 % de los pacientes que recibieron COMBO450 fueron: aumento de la concentración de gamma-glutamiltransferasa (GGT) elevada (9 %), concentración de creatina fosfocinasa (CPK) en la sangre (7 %), e hipertensión (6 %). La incidencia de cualquier grado de EI de interés, cuya definición se basa en las toxicidades comúnmente asociadas con los tratamientos inhibidores de MEK+BRAF comercializados, para los pacientes que recibieron COMBO450, incluye: exantema (23 %), pirexia (18 %), desprendimiento del epitelio pigmentario retiniano (13 %) y fotosensibilidad (5 %).  Los resultados completos de seguridad de la Parte 1 de COLUMBUS se presentaron en el Congreso Anual de la Sociedad para la Investigación de Melanoma del 2016.