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Diferentes estrategias informativas de las CCAA y el Gobierno de la Nación con relación a la COVID-19
Diferentes estretegias informativas han seguido las CCAA en el traslado a la población la información sobre la evolución de la epidemia de COVID-19. Unas han dado información con detalle hasta nivel de municipio sobre los casos y fallecimientos habidos en sus territorios ( Madrid, Cataluña, Andalucía, País Vasco, Murcia, Asturias, Cantabria, Canarias y Baleares) y el resto no han bajado del departamento de salud o de la provincia.
No entiendo qué razones puede tener un dirigente para no contar a sus administrados lo que está sucediendo con el mayor detalle, siempre que respete la privacidad de los enfermos, y ayude a que se conozca lo que nos ha estado enfermando y haciendo morir. Varias comunidades no han dado cifras en municipios menores de 200 habitantes, por salvar la privacidad de los pacientes. Quiero ver una actitud paternalista, pero creo que la información de lo que sucede, es el mejor antídoto contra las tan de actualidad "fake news".
Habló el gobierno de España de una total transparencia informativa en los indicadores que iban a permitir conducir la desescalada, pero se está produciendo en medio de situaciones de importantes divergencias entre gobiernos de CCAA y el del Estado por no haberse publicitado los indicadores y los rangos sobre los que basarse, por lo que no se podido entender el fundamento de las decisiones.
Informe favorable del CHMP de la EMA sobre Zolgensma
En su reunión del 26 Marzo de 2020, el Comité de Productos Medicinales para uso Humano (CHMP) adoptó una opinión positiva, recomendando la emisión de la autorización de comercialización de Zolgensma, que va dirigido al tratamiento de niños y jóvenes con Atrofia Muscular Espinal (SMA en inglés) del que nos hemos ocupado en varias ocasiones en este blog:
The clinical trial providing the main body of data for the assessment of Zolgensma was conducted in 22 patients who were less than six months of age at the time of the gene replacement therapy with Zolgensma. The trial assessed the percentage of patients who had improvement in their survival (i.e. without the need to be permanently on a ventilator) and motor milestones, such as head control, crawling, sitting, standing and walking (with or without assistance).
The survival of patients treated with Zolgensma exceeded what can be expected from untreated patients with severe SMA. Out of 22 patients enrolled in the trial, 20 patients (91%) were alive and did not need permanent ventilatory support at 14 months of age. The experience with this disease shows that at 14 months of age only 25% of patients are still alive. These patients also achieved motor milestones, which are usually not achieved in the natural history of the disease. 14 patients (64%) reached the milestone of independent sitting before 18 months of age. One patient (4%) reached the milestone of walking unassisted before reaching 16 months of age. Patients with less motor deterioration appeared to benefit the most from the treatment with Zolgensma.
El paso siguiente será la publicación del EPAR.
Han pasado varios meses desde la ultima autorización de comercialización de un MTA: Autorizado un nuevo ATMP: ZYNTEGLO en junio de 2019.
Tras una búsqueda en ClinicalTrialsRegister.eu con las palabra COVID VACCINE y no obtener ningún resultado, he buscado en clinicaltrials.gov y he obtenido estos cuatro resultados.
NCT
Brief Summary:
NCT04283461
This is a phase I, open-label, dose ranging clinical trial in males and non-pregnant females, 18 to 55 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273 manufactured by ModernaTX, Inc. mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized spike (S) protein of 2019-novel coronavirus (nCoV). Enrollment will occur at one domestic site. Forty-five subjects will be enrolled into one of three cohorts and will receive an intramuscular (IM) injection of mRNA-1273 on Days 1 and 29 in the deltoid muscle. Subjects will be followed through 12 months post second vaccination (Day 394). The primary objective is to evaluate the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 3 dosages in healthy adults.
NCT04299724
In December 2019, viral pneumonia (Covid-19) caused by a novel beta-coronavirus (SARS-CoV-2) broke out in Wuhan, China. Some patients rapidly progressed and suffered severe acute respiratory failure and died, making it imperative to develop a safe and effective vaccine to treat and prevent severe Covid-19 pneumonia. Based on detailed analysis of the viral genome and search for potential immunogenic targets, a synthetic minigene has been engineered based on conserved domains of the viral structural proteins and a polyprotein protease. The infection of Covid-19 is mediated through binding of the Spike protein to the ACEII receptor, and the viral replication depends on molecular mechanisms of all of these viral proteins. This trial proposes to develop universal vaccine and test innovative Covid-19 minigenes engineered based on multiple viral genes, using an efficient lentiviral vector system (NHP/TYF) to express viral proteins and immune modulatory genes to modify artificial antigen presenting cells (aAPC) and to activate T cells. In this study, the safety and immune reactivity of this aAPC vaccine will be investigated.
NCT04276896
In December 2019, viral pneumonia caused by a novel beta-coronavirus (Covid-19) broke out in Wuhan, China. Some patients rapidly progressed and suffered severe acute respiratory failure and died, making it imperative to develop a safe and effective vaccine to treat and prevent severe Covid-19 pneumonia. Based on detailed analysis of the viral genome and search for potential immunogenic targets, a synthetic minigene has been engineered based on conserved domains of the viral structural proteins and a polyprotein protease. The infection of Covid-19 is mediated through binding of the Spike protein to the ACEII receptor, and the viral replication depends on molecular mechanisms of all of these viral proteins. This trial proposes to develop and test innovative Covid-19 minigenes engineered based on multiple viral genes, using an efficient lentiviral vector system (NHP/TYF) to express viral proteins and immune modulatory genes to modify dendritic cells (DCs) and to activate T cells. In this study, the safety and efficacy of this LV vaccine (LV-SMENP) will be investigated.
NCT04292340
There is still no effective antiviral drugs and vaccines against SARS-CoV-2 yet now. This is an obsevational study, the investigators collected the clinical information and clinical outcomes of the COVID-19 patients using anti-2019-nCoV inactivated convalescent plasma.The study is to evaluate the efficacy and safety of anti-2019-nCoV inactivated convalescent plasma in the treatment of COVID-19 pneumonia.
Hoy, día 23 de febrero de 2020 se cumplen dos años desde la puesta en marcha de este blog. Dentro de un mes, el día 23 de marzo, hará 3 años del fallecimiento de mi hermano Guillermo. No hay día que no lo recuerde.
En este momento de no concesión de Autorizaciones de comercialización (MA´s) por la EMA desde junio de 2019 que concedió la de Zynteglo, espero que la recién (19 a 21 de febrero de 2020) pasada reunión del CAT haya alumbrado alguna MA
Aunque no sea tema del core del blog, la actual PHEIC sobre el Covid-19 declarada por la OMS el pasado día 30 de enero de 2020 que también vengo siguiendo -como de algún modo seguimos todos - me ha llevado a abrir una entrada sobre el brote que si bien descentra el blog, no me ha parecido adecuado iniciar otro blog sobre ello. Ahora son Lombardía y el Veneto, en Italia, los protagonista en la contención/resolución del problema.
Resultados de fase 1 del NCT03399448 de edición génica con CRISPR
De uno de los CT con edición génica que comenté en la entrada del día 27 de enero de 2020"Los PD-1 y CCR-5 los objetivos más deseados en los CT de edición génica", el ClinicalTrials.gov NCT03399448, se ha presentado resultados de fase 1.
En el artículo: CRISPR-engineered T cells in patients with refractory cancer de Stadtmauer et al, y entre ellos Carl H June, se describe el procedimiento de elaboración de NY-ESO-1 transduced CRISPR 3X edited cells (NYCE) y los resultados desde el punto de vista, sobre todo, de la seguridad.
El producto consiste en linfocitos T del paciente, modificados mediante CRISPR y tres gRNA para eliminar tres genes codificadores de los receptores TRAC, TRBC Y PD1. Además, mediante vector viral modifican el gen NY-ESO-1
Copio del artículo:
Experimental design
Guide RNAs (gRNA)
The genomic gRNA target sequences with PAM in bold were: TRAC1 and TRAC2: 5’-TGTGCTAGACATGAGGTCTATGG-3’, TRBC: 5’-GGAGAATGACGAGTGGACCCAGG-3’, and PDCD1: 5’-GGCGCCCTGGCCAGTCGTCTGGG-3
Lentiviral vector manufacturing
The 8F TCR recognizes the HLA-A*0201 SLLMWITQC epitope on NY-ESO-1 and LAGE-1. The 8F TCR was isolated from a T cell clone obtained from patient after vaccination with NY-ESO-1 peptide. The TCR sequences were cloned into a transfer plasmid that contains the EF-1α promoter, a cPPT sequence, a rev response element and a woodchuck hepatitis virus posttranscriptional regulatory element
El proceso de manufactura se refleja en este gráfico
Y el protocolo del CT
En resumen:
In conclusion, our phase I human pilot study has confirmed that multiplex CRISPR-Cas9 editing of the human genome is possible at clinical scale. We note that while the initial clinical results are safe, experience with more patients given infusions with higher editing efficiencies and longer observation after infusion will be required to fully assess the safety of this approach. The potential rejection of infused cells due to pre-existing immune responses to Cas9 (28, 29) does not appear to be a barrier to the application of this promising technology. Finally, it is important to note that our manufacturing was based on the reagents available in 2016, when our protocol had been reviewed by the NIH Recombinant DNA Advisory Committee and received approval. Our Investigational New Drug Application was subsequently reviewed and accepted by the U.S. FDA. There has been rapid progress in the field since that time, with the development of reagents that should increase efficiencies and decrease off-target editing using CRISPR-based technology (50).
Of the three patients that were infused with CRISPR-Cas9 engineered T cells, two patients had refractory advanced myeloma and one patient had a refractory metastatic sarcoma not responding to multiple prior therapies
