RESUMEN
Importance: After US Food and Drug Administration (FDA) approval of a new drug, sponsors can submit additional clinical data to obtain supplemental approval for use for new indications. Objective: To characterize pivotal trials supporting recent supplemental new indication approvals of drugs and biologics by the FDA and to compare them with pivotal trials that supported these therapeutics' original indication approvals. Design, Setting, and Participants: This is a cross-sectional study characterizing pivotal trials supporting supplemental indication approvals by the FDA between 2017 and 2019 and pivotal trials that supported these therapeutics' original indication approvals. Data analysis was performed from August to October 2020. Main Outcomes and Measures: Number and design of pivotal trials supporting both supplemental and original indication approvals. Results: From 2017 to 2019, the FDA approved 146 supplemental indications for 107 therapeutics on the basis of 181 pivotal efficacy trials. The median (interquartile range) number of trials per supplemental indication was 1 (1-1). Most trials used either placebo (77 trials [42.5%; 95% CI, 35.6%-49.8%]) or active comparators (65 trials [35.9%; 95% CI, 29.3%-43.1%]), and most of these multigroup trials were randomized (141 trials [99.3%; 95% CI, 96.0%-100.0%]) and double-blinded (106 trials [74.5%; 95% CI, 66.6%-81.0%]); 80 trials (44.2%; 95 CI, 37.2%-51.5%) used clinical outcomes as the primary efficacy end point. There was no difference between oncology therapies and those approved for other therapeutic areas to have supplemental indication approvals be based on at least 2 pivotal trials (11.5% vs 20.6%; difference, 9.1%; 95% CI, 2.9%-21.0%; P = .10). Similarly, there was no difference in use of randomization (98.3% vs 100.0%; difference, 1.7%; 95% CI, 1.6%-5.0%; P = .43) among multigroup trials, although these trials were less likely to be double-blinded (50.8% vs 92.3%; difference, 41.5%; 95% CI, 27.4%-55.5%; P < .001); overall, these trials were less likely to use either placebo or active comparators (64.9% vs 86.7%; difference, 21.8% 95% CI, 9.8%-33.9%; P < .001) or to use clinical outcomes as their primary efficacy end point (27.5% vs 61.1%; difference, 33.6%; 95% CI, 14.1%-40.9%; P < .001) and were longer (median [interquartile range], 17 [6-48] weeks vs 95 [39-146] weeks). Original approvals were more likely than supplemental indication approvals to be based on at least 2 pivotal trials (44.0% [95% CI, 33.7%-42.6%] vs 15.8% [95% CI, 10.7%-22.5%]; difference, 28.2%; 95% CI, 17.6%-39.6%; P < .001) and less likely to be supported by at least 1 trial of 12 months' duration (27.6% [95% CI, 17.9%-35.0%] vs 54.8% [95% CI, 46.7%-62.6%]; difference, 27.2%; 95% CI, 14.5%-37.8%; P < .001). Pivotal trial designs were otherwise not significantly different. Conclusions and Relevance: These findings suggest that the number and design of the pivotal trials supporting supplemental indication approvals by the FDA varied across therapeutic areas, with the strength of evidence for cancer indications weaker than that for other indications. There was little difference in the design characteristics of the pivotal trials supporting supplemental indication and original approvals.
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Productos Biológicos/normas , Estudios Clínicos como Asunto/normas , Aprobación de Drogas/métodos , Reposicionamiento de Medicamentos/normas , Medicamentos bajo Prescripción/normas , Proyectos de Investigación/normas , United States Food and Drug Administration/normas , Estudios Clínicos como Asunto/estadística & datos numéricos , Estudios Transversales , Humanos , Proyectos de Investigación/estadística & datos numéricos , Estados Unidos , United States Food and Drug Administration/estadística & datos numéricosRESUMEN
SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2'-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (nâ¯=â¯5903). The screening was performed against viral targets using three sequential docking modes (i.e., HTVS, SP, and XP). Virtual screening identified â¼290 potential inhibitors based on the criteria of energy, docking parameters, ligand, and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. The top lead from each target pool was further subjected to molecular dynamics simulation using the Desmond module. The resulting top eight hits were tested for their SARS-CoV-2 anti-viral activity in-vitro. Among these, a known inhibitor of protein kinase C isoforms, Bisindolylmaleimide IX (BIM IX), was found to be a potent inhibitor of SARS-CoV-2. Further, target validation through enzymatic assays confirmed 3CLpro to be the target. This is the first study that has showcased BIM IX as a COVID-19 inhibitor thereby validating our pipeline.
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Antivirales/administración & dosificación , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Sistemas de Liberación de Medicamentos/normas , Indoles/administración & dosificación , Maleimidas/administración & dosificación , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/enzimología , Antivirales/metabolismo , Proteasas 3C de Coronavirus/química , Proteasas 3C de Coronavirus/metabolismo , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos/métodos , Evaluación Preclínica de Medicamentos/métodos , Reposicionamiento de Medicamentos/métodos , Reposicionamiento de Medicamentos/normas , Ensayos Analíticos de Alto Rendimiento/métodos , Ensayos Analíticos de Alto Rendimiento/normas , Humanos , Indoles/química , Indoles/metabolismo , Maleimidas/química , Maleimidas/metabolismo , Simulación del Acoplamiento Molecular/métodos , Simulación del Acoplamiento Molecular/normas , Estructura Secundaria de Proteína , Reproducibilidad de los Resultados , SARS-CoV-2/químicaRESUMEN
Cardiovascular outcome trials in patients with type 2 diabetes at high cardiovascular risk have led to remarkable advances in our understanding of the effectiveness of GLP-1 receptor agonists and SGLT2 inhibitors to reduce cardiorenal events. In 2019, the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), and European Society of Cardiology (ESC) published updated recommendations for the management of such patients. We are concerned that ongoing discussions focusing on the differences between the endocrinologists' consensus report from the ADA and EASD and cardiologists' guidelines from the ESC are contributing to clinical inertia, thereby effectively denying evidence-based treatments advocated by both groups to patients with type 2 diabetes and cardiorenal disease. A subset of members from the writing groups of the ADA-EASD consensus report and the ESC guidelines was convened to emphasise where commonalities exist and to propose an integrated framework that encompasses the views incorporated in management approaches proposed by the ESC and the ADA and EASD. Coordinated action is required to ensure that people with type 2 diabetes, cardiovascular disease, heart failure, or chronic kidney disease are treated appropriately with an SGLT2 inhibitor or GLP-1 receptor agonist. In our opinion, this course should be initiated independent of background therapy, current glycaemic control, or individualised treatment goals.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Drogas en Investigación/uso terapéutico , Guías de Práctica Clínica como Asunto/normas , Consenso , Reposicionamiento de Medicamentos/métodos , Reposicionamiento de Medicamentos/normas , Práctica Clínica Basada en la Evidencia/métodos , Práctica Clínica Basada en la Evidencia/normas , Humanos , Hipoglucemiantes/uso terapéutico , Individualidad , Planificación de Atención al Paciente/normas , Sociedades Médicas/normasRESUMEN
Much has changed in the medical treatment of COVID-19 after the first patient with an infection with SARS-CoV-2 in the Netherlands was diagnosed in February 2020. On the basis of limited data, at first only off-label use of (hydroxy)chloroquine seemed to be a treatment option. However, now based on the findings of several randomized studies, other medicines have been included in the Dutch guidelines about the treatment of COVID-19. In this article, we will briefly discuss the current state of affairs with regard to the drugs (hydroxy) chloroquine, remdesivir and corticosteroids. Again, it appears that only well-executed randomized clinical trials can determine the status of various supposedly effective drugs.
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Tratamiento Farmacológico de COVID-19 , COVID-19 , Reposicionamiento de Medicamentos , Glucocorticoides , Hidroxicloroquina , SARS-CoV-2/efectos de los fármacos , Adenosina Monofosfato/farmacología , Adenosina Monofosfato/uso terapéutico , Alanina/farmacología , Alanina/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , COVID-19/epidemiología , Reposicionamiento de Medicamentos/métodos , Reposicionamiento de Medicamentos/normas , Glucocorticoides/farmacología , Glucocorticoides/uso terapéutico , Humanos , Hidroxicloroquina/farmacología , Hidroxicloroquina/uso terapéutico , Países Bajos/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoAsunto(s)
Tratamiento Farmacológico de COVID-19 , Aprobación de Drogas/legislación & jurisprudencia , Reposicionamiento de Medicamentos/normas , Drogas en Investigación/uso terapéutico , Seguridad del Paciente/normas , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Amidas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , COVID-19/epidemiología , COVID-19/mortalidad , Ensayos Clínicos Fase III como Asunto , Ensayos Clínicos Controlados como Asunto/normas , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , India/epidemiología , Placebos , Pirazinas/uso terapéutico , Reproducibilidad de los Resultados , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/patogenicidad , Factores de Tiempo , Estados Unidos/epidemiología , Esparcimiento de Virus/efectos de los fármacosRESUMEN
The unprecedented global scale of COVID-19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarize the evidence for antiretrovirals to treat COVID-19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.
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Antirretrovirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos , Neumonía Viral/tratamiento farmacológico , Investigación/normas , COVID-19 , Infecciones por Coronavirus/prevención & control , Combinación de Medicamentos , Reposicionamiento de Medicamentos/normas , Reposicionamiento de Medicamentos/tendencias , Humanos , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , Pandemias/prevención & control , Neumonía Viral/prevención & control , Investigación/tendencias , Ritonavir/uso terapéutico , SARS-CoV-2 , Tenofovir/uso terapéutico , Factores de TiempoAsunto(s)
Cloroquina/farmacología , Infecciones por Coronavirus , Aprobación de Drogas/legislación & jurisprudencia , Reposicionamiento de Medicamentos , Hidroxicloroquina/farmacología , Pandemias , Neumonía Viral , Autorización Previa , Acceso a la Información , Antimaláricos/farmacología , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Reposicionamiento de Medicamentos/métodos , Reposicionamiento de Medicamentos/normas , Reposicionamiento de Medicamentos/tendencias , Medicina Basada en la Evidencia , Humanos , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Autorización Previa/legislación & jurisprudencia , Autorización Previa/tendencias , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19RESUMEN
Potential treatments for coronavirus disease 2019 (COVID-19) are being investigated at unprecedented speed, and successful treatments will rapidly be used in tens or hundreds of thousands of patients. To ensure safe and effective use in all those patents it is essential also to develop, at unprecedented speed, a means to provide frequently updated, optimal dosing information for all patient subgroups. Success will require immediate collaboration between drug developers, academics, and regulators.
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Antivirales , Infecciones por Coronavirus , Relación Dosis-Respuesta a Droga , Desarrollo de Medicamentos , Reposicionamiento de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Pandemias , Neumonía Viral , Antivirales/farmacocinética , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Disponibilidad Biológica , Biomarcadores Farmacológicos/análisis , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Desarrollo de Medicamentos/métodos , Desarrollo de Medicamentos/normas , Cálculo de Dosificación de Drogas , Monitoreo de Drogas/normas , Reposicionamiento de Medicamentos/métodos , Reposicionamiento de Medicamentos/normas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Humanos , Cooperación Internacional , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , SARS-CoV-2 , Resultado del TratamientoRESUMEN
The major impact produced by the severe acute respiratory syndrome coronavirus 2 (SARSCoV2) focused many researchers attention to find treatments that can suppress transmission or ameliorate the disease. Despite the very fast and large flow of scientific data on possible treatment solutions, none have yet demonstrated unequivocal clinical utility against coronavirus disease 2019 (COVID19). This work represents an exhaustive and critical review of all available data on potential treatments for COVID19, highlighting their mechanistic characteristics and the strategy development rationale. Drug repurposing, also known as drug repositioning, and target based methods are the most used strategies to advance therapeutic solutions into clinical practice. Current in silico, in vitro and in vivo evidence regarding proposed treatments are summarized providing strong support for future research efforts.
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Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos , Neumonía Viral/tratamiento farmacológico , Internalización del Virus/efectos de los fármacos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/clasificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Enzima Convertidora de Angiotensina 2 , Betacoronavirus/patogenicidad , Betacoronavirus/fisiología , Bromhexina/farmacología , Bromhexina/uso terapéutico , COVID-19 , Clorpromazina/farmacología , Clorpromazina/uso terapéutico , Ensayos Clínicos como Asunto/métodos , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/mortalidad , Diminazeno/farmacología , Diminazeno/uso terapéutico , Reposicionamiento de Medicamentos/métodos , Reposicionamiento de Medicamentos/normas , Reposicionamiento de Medicamentos/tendencias , Ésteres , Gabexato/análogos & derivados , Gabexato/farmacología , Gabexato/uso terapéutico , Guanidinas , Humanos , Pandemias , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Peptidil-Dipeptidasa A/uso terapéutico , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Receptor de Angiotensina Tipo 1/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/uso terapéutico , SARS-CoV-2 , Transducción de Señal/efectos de los fármacosAsunto(s)
Inteligencia Artificial , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/terapia , Desarrollo de Medicamentos , Aprendizaje Automático , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/terapia , Betacoronavirus , COVID-19 , Vacunas contra la COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Susceptibilidad a Enfermedades/diagnóstico , Desarrollo de Medicamentos/normas , Desarrollo de Medicamentos/tendencias , Reposicionamiento de Medicamentos/normas , Humanos , SARS-CoV-2 , Vacunas Virales/análisis , Tratamiento Farmacológico de COVID-19RESUMEN
Prescription pattern of rescue medication like intranasal midazolam (INM) for domiciliary management of seizure is highly variable. The present cross-sectional study was designed to determine the impact of the use of INM on healthcare utilization by those who used INM when compared with those who are not on any rescue medications in a resource-constraint setting. Children with epilepsy aged 1-14â¯years who have used INM to abort seizure at home (INM group) were compared with those who have not used INM (control group). The baseline demographic and seizure characteristics including the severity of epilepsy were comparable between the INM group (nâ¯=â¯50) and controls (nâ¯=â¯50). The INM group had significantly better knowledge of the correct method of administration when compared with controls [43 (86%) vs. 17 (34%); pâ¯<â¯0.01]. Seizures were aborted in 36 (72%) users in the INM group; of the rest of 14 children, 4 (8%) used it for the second time. The median Interquartile range (IQR) time taken to abort the seizure was 2.5 (1.0, 5.2) min. The need for intensive care admissions was comparable between the INM group and control group, although the number of emergency visits was significantly higher in the former [2.9 vs. 1.4, pâ¯=â¯0.04]. Despite comparable severity of epilepsy and better knowledge of its correct use, children who were prescribed INM required more hospital emergency visits. This study with a limited sample size prompts us to introspect the practice of INM for children with epilepsy.
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Manejo de la Enfermedad , Prescripciones de Medicamentos , Epilepsia/tratamiento farmacológico , Servicios de Atención de Salud a Domicilio , Midazolam/administración & dosificación , Convulsiones/tratamiento farmacológico , Administración Intranasal , Adolescente , Niño , Preescolar , Estudios Transversales , Prescripciones de Medicamentos/normas , Reposicionamiento de Medicamentos/métodos , Reposicionamiento de Medicamentos/normas , Servicio de Urgencia en Hospital , Epilepsia/diagnóstico , Femenino , Servicios de Atención de Salud a Domicilio/normas , Humanos , Hipnóticos y Sedantes/administración & dosificación , Lactante , Masculino , Convulsiones/diagnósticoRESUMEN
BACKGROUND: Despite years of success of most anti-cancer drugs, one of the major clinical problems is inherent and acquired resistance to these drugs. Overcoming the drug resistance or developing new drugs would offer promising strategies in cancer treatment. Disulfiram, a drug currently used in the treatment of chronic alcoholism, has been found to have anti-cancer activity. OBJECTIVE: To summarize the anti-cancer effects of Disulfiram through a thorough patent review. METHODS: This article reviews molecular mechanisms and recent patents of Disulfiram in cancer therapy. RESULTS: Several anti-cancer mechanisms of Disulfiram have been proposed, including triggering oxidative stress by the generation of reactive oxygen species, inhibition of the superoxide dismutase activity, suppression of the ubiquitin-proteasome system, and activation of the mitogen-activated protein kinase pathway. In addition, Disulfiram can reverse the resistance to chemotherapeutic drugs by inhibiting the P-glycoprotein multidrug efflux pump and suppressing the activation of NF-kB, both of which play an important role in the development of drug resistance. Furthermore, Disulfiram has been found to reduce angiogenesis because of its metal chelating properties as well as its ability to inactivate Cu/Zn superoxide dismutase and matrix metalloproteinases. Disulfiram has also been shown to inhibit the proteasomes, DNA topoisomerases, DNA methyltransferase, glutathione S-transferase P1, and O6- methylguanine DNA methyltransferase, a DNA repair protein highly expressed in brain tumors. The patents described in this review demonstrate that Disulfiram is useful as an anti-cancer drug. CONCLUSION: For years the FDA-approved, well-tolerated, inexpensive, orally-administered drug Disulfiram was used in the treatment of chronic alcoholism, but it has recently demonstrated anti-cancer effects in a range of solid and hematological malignancies. Its combination with copper at clinically relevant concentrations might overcome the resistance of many anti-cancer drugs in vitro, in vivo, and in patients.
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Antineoplásicos/uso terapéutico , Disulfiram/uso terapéutico , Reposicionamiento de Medicamentos , Patentes como Asunto , Animales , Antineoplásicos/economía , Disulfiram/economía , Reposicionamiento de Medicamentos/economía , Reposicionamiento de Medicamentos/métodos , Reposicionamiento de Medicamentos/normas , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/terapia , Especies Reactivas de Oxígeno/metabolismoAsunto(s)
Anticonvulsivantes/uso terapéutico , Reposicionamiento de Medicamentos/métodos , Epilepsias Mioclónicas/tratamiento farmacológico , Fenfluramina/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , Reposicionamiento de Medicamentos/normas , Epilepsias Mioclónicas/genética , Femenino , Fenfluramina/administración & dosificación , Fenfluramina/efectos adversos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Canal de Sodio Activado por Voltaje NAV1.1 , Adulto JovenAsunto(s)
Reposicionamiento de Medicamentos , Accesibilidad a los Servicios de Salud , Síndromes Miasténicos Congénitos/tratamiento farmacológico , Albuterol/uso terapéutico , Inhibidores de la Colinesterasa/uso terapéutico , Reposicionamiento de Medicamentos/métodos , Reposicionamiento de Medicamentos/normas , Efedrina/uso terapéutico , Accesibilidad a los Servicios de Salud/organización & administración , Accesibilidad a los Servicios de Salud/normas , Humanos , Uso Fuera de lo Indicado , Pautas de la Práctica en Medicina/organización & administración , Pautas de la Práctica en Medicina/normas , Calidad de Vida , Quinidina/uso terapéutico , Terapias en Investigación/métodos , Resultado del TratamientoRESUMEN
AIMS: The anthelminthic ivermectin is receiving new attention as it is being repurposed for new indications such as mass drug administrations for the treatment of scabies or in malaria vector control. As its pharmacokinetics are still poorly understood, we aimed to characterize the population pharmacokinetics of ivermectin in plasma and dried blood spots (DBS), a sampling method better suited to field trials, with special focus on the influence of body composition and enterohepatic circulation. METHODS: We performed a clinical trial in 12 healthy volunteers who each received a single oral dose of 12 mg ivermectin, and collected peripheral venous and capillary DBS samples. We determined ivermectin concentrations in plasma and DBS by liquid chromatography tandem mass spectrometry using a fully automated and scalable extraction system for DBS sample processing. Pharmacokinetic data were analysed using non-linear mixed effects modelling. RESULTS: A two-compartment model with a transit absorption model, first-order elimination, and weight as an influential covariate on central volume of distribution and clearance best described the data. The model estimates (inter-individual variability) for a 70 kg subject were: apparent population clearance 7.7 (25%) l h-1 , and central and peripheral volumes of distribution 89 (10%) l and 234 (20%) l, respectively. Concentrations obtained from DBS samples were strongly linearly correlated (R2 = 0.97) with plasma concentrations, and on average 30% lower. CONCLUSION: The model accurately depicts population pharmacokinetics of plasma and DBS concentrations over time for oral ivermectin. The proposed analytical workflow is scalable and applicable to the requirements of mass drug administrations.
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Antiparasitarios/farmacocinética , Pruebas con Sangre Seca , Ivermectina/farmacocinética , Administración Oral , Adulto , Antiparasitarios/administración & dosificación , Reposicionamiento de Medicamentos/normas , Estudios de Factibilidad , Femenino , Voluntarios Sanos , Humanos , Ivermectina/administración & dosificación , Malaria/prevención & control , Masculino , Administración Masiva de Medicamentos/normas , Modelos Biológicos , Mosquitos Vectores/efectos de los fármacos , Escabiosis/tratamiento farmacológico , Factores de Tiempo , Adulto JovenRESUMEN
Drug repurposing has been proposed as a strategy to develop new therapies that has fewer risks, lower costs and shorter timelines than developing completely new drugs. However, the potential of this strategy has not been as widely realized as hoped, in part owing to legal and regulatory barriers. Here, we highlight these barriers and consider how they could be overcome.
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Atención a la Salud/legislación & jurisprudencia , Reposicionamiento de Medicamentos/normas , Regulación Gubernamental , Práctica Clínica Basada en la Evidencia , HumanosRESUMEN
Given the high attrition rates, substantial costs and slow pace of new drug discovery and development, repurposing of 'old' drugs to treat both common and rare diseases is increasingly becoming an attractive proposition because it involves the use of de-risked compounds, with potentially lower overall development costs and shorter development timelines. Various data-driven and experimental approaches have been suggested for the identification of repurposable drug candidates; however, there are also major technological and regulatory challenges that need to be addressed. In this Review, we present approaches used for drug repurposing (also known as drug repositioning), discuss the challenges faced by the repurposing community and recommend innovative ways by which these challenges could be addressed to help realize the full potential of drug repurposing.
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Descubrimiento de Drogas , Industria Farmacéutica , Reposicionamiento de Medicamentos/normas , HumanosRESUMEN
Biosimilars have demonstrated their equivalence with biologic originators, according to rigorous specifications imposed by the regulatory agencies, the FDA and the EMA. Their development is justified by the very high cost of biopharmaceuticals, and strong incentives for their prescription lead us to hope substantial savings, allowing to finance other innovative molecules. Trastuzumab marked history of the treatment of breast cancer. Four biosimilars of trastuzumab are available for routine use and we will detail the key points of their development.
TITLE: Anticorps biosimilaires versus princeps - L'expérience en rhumatologie et les biosimilaires du trastuzumab en oncologie. ABSTRACT: Les biosimilaires sont des produits ayant montré leur équivalence avec le traitement biologique de référence, selon un cahier des charges strict imposé par les agences d'enregistrement, la FDA et l'EMA. Leur développement et leur utilisation sont justifiés par le coût très élevé des biomédicaments, et de fortes incitations à leur prescription font espérer des économies substantielles, permettant le financement d'autres molécules innovantes. Le trastuzumab a marqué l'histoire des traitements du cancer du sein, quatre biosimilaires étant désormais disponibles pour une utilisation en routine. Nous détaillerons ici les points clés de leur développement.