Comenzaron en el Sanatorio Güemes los ensayos con suero equino en pacientes con Covid-19. Evaluarán la seguridad y eficacia del que podría ser el primer medicamento argentino para la enfermedad.
Luego de la aprobación de la ANMAT a la investigación para el estudio clínico del suero equino hiperinmune, un tratamiento de los más avanzados contra la enfermedad Covid-19 que causó la pandemia mundial actual, comenzaron los ensayos en humanos en el Sanatorio Güemes.
El suero equino hiperinmune se suma así oficialmente a otros tratamientos en estudio en humanos que están en experimentación, como el uso de antiinflamatorios, los antivirales, plasma de convalecientes y más.
El suero anti-COVID-19 es el primer potencial medicamento innovador para el tratamiento de la infección por el nuevo coronavirus totalmente desarrollado en Argentina. En ensayos in vitro demostró la capacidad de neutralizar el virus, con una potencia alrededor de 50 veces mayor que el promedio del plasma de convalecientes.
¿Es el suero equino hiperinmune capaz de neutralizar el virus SARS-CoV-2? La secuencia de su hallazgo es compleja pero breve: el caballo por naturaleza tiene una gran capacidad para generar anticuerpos. Existe un antígeno -extraído por ingeniería genética de la proteína RDB del virus SARS-CoV-2- que genera muchísimos anticuerpos cuando se lo inyecta al caballo. El objetivo del hallazgo científico es extraer un suero masivo y potente que luego pueda ser usado como protección para los humanos ante el COVID-19.
Es la misma estrategia que se usó para la vacuna recombinante de la Hepatitis B. Y además la producción de sueros equinos hiperinmunes se utiliza desde hace años para el tratamiento contra el veneno de serpientes y alacranes o contra la toxina tetánica o contra el botulismo.
El laboratorio Inmunova -ubicado en la Fundación Argentina de Nanotecnología (FAN), en la Universidad de San Martín (UNSAM), anunció que la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) aprobó el protocolo de investigación del estudio clínico de Fase 2/3 del suero hiperinmune anti-COVID-19, que evaluará su seguridad y eficacia en el tratamiento de pacientes con infección por SARS-CoV-2.
“Cuando empezó la pandemia, Inmunova ya estaba trabajando en el desarrollo de un suero de estas características para tratar el Síndrome Urémico Hemolítico (SUH), que es otra enfermedad mucho menos frecuente que el coronavirus, pero muy importante en la Argentina. Ya estábamos en fases clínicas avanzadas y vimos la oportunidad de adaptarlo al COVID-19, como una forma importante de producir una gran cantidad de anticuerpos para una terapia pasiva de alta efectividad, y con una tecnología, simple y robusta. En 70 días con un grupo inmenso académico de tres empresas logramos desarrollar un suero hiperinmune, y demostramos junto al laboratorio nacional de referencia, el Instituto Malbrán, dirigido por la doctora Elsa Baumeister que nuestro suero tiene un potencial neutralizante, es decir, la capacidad de frenar al virus”, explicó al portal de noticias porteño Infobae el doctor Fernando Goldbaum, director científico de Inmunova e investigador superior del CONICET.
Goldbaum, que también es jefe del Laboratorio de Inmunología y Microbiología Molecular en la Fundación Instituto Leloir, detalló que “el virus entra en las células a través de una proteína que se une a un receptor para ingresar. Nosotros usamos ese pedacito de virus para inmunizar caballos y obtuvimos un título altísimo de anticuerpos contra esa proteína. Lo que demostramos en este ensayo es que estos anticuerpos tienen una capacidad muy grande de evitar que el virus entre a las células”.
Linus Spatz, biólogo, socio fundador y director de Inmunova, Grupo Insud, remarcó: “Lo que pudimos demostrar -hasta hora in vitro- es que los anticuerpos que estamos produciendo -que técnicamente son fragmentos de anticuerpos, no son anticuerpos enteros, así evitamos cualquier efecto adverso que pueda venir de un anticuerpo equino. En tres laboratorios distintos que lo midieron, demostraron que fueron capaces de neutralizar con muchísima potencia este virus. Es decir que lo que logramos probar, tanto en el Instituto Malbrán como en la Facultad de Medicina de Córdoba y en la Fundación Leloir es que estos anticuerpos bloquean el ingreso del virus a las células. En ese caso estaríamos frenando el desarrollo de la enfermedad y esa es la gran esperanza de entrar ahora en ensayos clínicos -será en principio en pacientes moderados – que no estén con necesidad de internación en una Unidad de Cuidados Intensivos (UCI) y que realmente frenemos el desarrollo de la enfermedad”.
Y agregó: “Conceptualmente el plasma de convalecientes y el suero hiperinmune son terapias parecidas, en los dos casos son terapias pasivas. Quiere decir que uno extrae anticuerpos de un organismo y se los da al paciente que los necesita. En ese sentido estamos basándonos en la misma evidencia científica hasta ahora. Tal vez la ventaja que tiene el suero equino hiperinmune es la escalabilidad relativamente rápida, uno puede inmunizar 10 caballos, se vacunan los caballos, con una partícula, un antígeno técnicamente del virus; nunca se enferman los caballos, es como cualquier otra vacunación, entonces uno puede hacer 10, 100 o 200 sueros si hace falta para abastecer a toda la demanda depende como se va dando la pandemia. Respecto a la potencia, in vitro por el momento, nuestros sueros mostraron una capacidad alta de neutralización. Ahora habrá que probarlo en la fase clínica en los pacientes, siempre nosotros nos basamos en evidencias”.
Comienzo del estudio clínico
El estudio clínico comienza esta semana en el Sanatorio Güemes, en el Hospital General de Agudos “Dr. Ignacio Pirovano”, ambos de CABA, en el Hospital Cuenca Alta – SAMIC de Cañuelas y en el Instituto Médico Platense de La Plata. Próximamente iniciará en más de diez hospitales y clínicas de obras sociales del área metropolitana de Buenos Aires y La Plata. Incluye la participación voluntaria de 242 pacientes adultos con enfermedad moderada a severa causada por la infección del SARS-CoV-2 confirmada por PCR, dentro de los diez días del inicio de síntomas y que requieren hospitalización.
Dicho estudio clínico de Fase 2/3 aprobado por ANMAT busca demostrar la seguridad y eficacia del suero hiperinmune en términos de mejoría clínica del paciente: la recuperación pronta para poder ser externado, que no avance la enfermedad y por tanto la necesidad de asistencia respiratoria mecánica o el traslado a una unidad de cuidado intensivo.
Este suero terapéutico es una inmunoterapia basada en anticuerpos policlonales equinos, obtenidos mediante la inyección de una proteína recombinante del SARS-CoV-2 en estos animales, inocua para ellos, que hace que generen gran cantidad de anticuerpos neutralizantes. Luego de la extracción del plasma –un proceso similar al que se utiliza cuando se extrae plasma de personas (plasmaféresis)– estos anticuerpos se purifican y procesan, a través de un proceso biotecnológico, para obtener fragmentos de los anticuerpos con alta pureza y buen perfil de seguridad.
El suero producido contiene gran cantidad de estos anticuerpos con capacidad neutralizante, es decir, que podría evitar que el virus ingrese a las células que es donde se multiplica. Ha sido desarrollado para inmunización pasiva, es decir, que al paciente se le administran anticuerpos contra el agente infeccioso, produciendo su bloqueo y evitando que se propague. Esta estrategia terapéutica es similar a la del plasma de personas que se recuperaron del COVID-19, pero en este caso los anticuerpos se obtienen de plasma equino. Esto posibilita que la producción del suero terapéutico a partir de este plasma pueda escalarse en cantidad.
Los anticuerpos policlonales equinos se utilizan para la elaboración de medicamentos, atender emergencias médicas como el envenenamiento por mordedura de serpientes y alacranes, intoxicaciones por toxina tetánica, botulismo, exposición al virus de la rabia y enfermedades infecciosas como la influenza aviar.
“Si los resultados son los esperados, el suero hiperinmune presenta la ventaja de que puede ser producido a gran escala. Además contamos con el asesoramiento de un comité de expertos, que va a monitorear la seguridad y los resultados del ensayo clínico”, concluyó Spatz.
Este posible tratamiento para hacer frente al COVID-19 es fruto del trabajo encabezado por Inmunova, Grupo Insud, y el Instituto Biológico Argentino (BIOL)
Con la colaboración conjunta de la:
- Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS)
- Fundación Instituto Leloir (FIL)
- Mabxience
- CONICET
- Universidad Nacional de San Martín (UNSAM)
- Instituto de Virología “Dr. José M. Vanella” (UN de Córdoba)
Y cuenta con el apoyo de la Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación.
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