RESUMO
This cross-sectional study evaluates the use of the US Food and Drug Administration's Real-Time Oncology Review (RTOR) program in confirming the effectiveness of cancer drugs.
Assuntos
Aprovação de Drogas, Vigilância de Produtos Comercializados, United States Food and Drug Administration, Humanos, Vigilância de Produtos Comercializados/métodos, Vigilância de Produtos Comercializados/estatística & dados numéricos, Vigilância de Produtos Comercializados/normas, Estados Unidos, Oncologia, Neoplasias/tratamento farmacológico, Antineoplásicos/uso terapêuticoRESUMO
Since the late 1950s, radiopharmaceuticals have been used for diagnosis and treatment in clinical nuclear medicine in China. Over the decades, China has successfully established a relatively sophisticated system for radiopharmaceutical production and management, supported by state-of-the-art facilities. With the rapid growth of the national economy, the radiopharmaceutical market in China is expanding at a remarkable pace. This burgeoning market has led to an escalating demand for clinical-stage radiopharmaceuticals, either produced domestically or imported. Despite this positive trajectory, the development and application of radiopharmaceuticals in China have been hindered by several challenges that persist, such as inadequate research, insufficient investment, limited availability of radionuclides, shortage of trained personnel in related fields, and imperfections in policies and regulations. In an exciting development, the regulation reforms implemented since 2015 have positively affected China's drug regulatory system. The introduction of the "Mid- and Long-Term Development Plan (2021-2035) for Medical Isotopes" created concurrently an opportune environment for the advancement of innovative radiopharmaceuticals. In this review, we aim to provide an overview of the approval process for novel radiopharmaceuticals by the National Medical Products Administration and the status of radiopharmaceuticals in research and development in China. Preclinical development and clinical translation of radiopharmaceuticals are undergoing rapid evolution in China. As practitioners in the field in China, we provide several practical suggestions to stimulate open discussions and thoughtful consideration.
Assuntos
Aprovação de Drogas, Compostos Radiofarmacêuticos, Compostos Radiofarmacêuticos/uso terapêutico, China, HumanosRESUMO
INTRODUCTION: Adult patients and clinicians are faced with several pharmacological options to manage attention-deficit/hyperactivity disorder (ADHD). If types or rates of adverse experiences vary among these options, these differences could inform the shared decision-making process. METHODS: To discern differentiating evidence-based patterns of risk, we analyzed data from FDA package labels for drugs approved to treat adult ADHD and reports from the registration trials used to create these labels. Three analyses of adverse effects were conducted: placebo-corrected occurrence at rates of 1 in 5, 10, and 20 participants, association with discontinuation, and uniqueness of occurrence within the treatment options. RESULTS: Among the 7 agents approved to treat adult ADHD, the number of types of side effects experienced during a mix of fixed and flexible-dose studies was greatest among the nonstimulant medications, but the stimulant medications had higher rates of occurrence of side effects. The minimum frequency at which all medications had adverse events was 1 in 10 participants. Overall discontinuation rates did not differ among the stimulant medications nor between stimulants and nonstimulants. DISCUSSION: To our knowledge, this is the first study to compile and compare data from all FDA registration trials for medications approved to treat adult ADHD. This article describes a process by which readily available adverse event reporting data can be used as a tool to inform shared clinical decision-making. While differences in the methodology and outcome reporting of the trials included may limit generalizability, the number of individual patients included and the completeness of the discontinuation data can be used to inform discussions with patients about the relative likelihood of adverse experiences and other patient concerns.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade, Estimulantes do Sistema Nervoso Central, Tomada de Decisão Compartilhada, United States Food and Drug Administration, Humanos, Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico, Estados Unidos, Estimulantes do Sistema Nervoso Central/efeitos adversos, Adulto, Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos, Aprovação de DrogasRESUMO
Five drugs are now approved or in trials for genetic condition that triggers misplaced bone growth.
Assuntos
Desenvolvimento de Medicamentos, Doenças Raras, Humanos, Doenças Raras/tratamento farmacológico, Doenças Raras/genética, Doenças Ósseas/tratamento farmacológico, Aprovação de Drogas, Anticorpos Monoclonais, Compostos de BifeniloRESUMO
Drugs have structural homology across similar biological targets. Small molecule drugs have the efficacy to target specific molecular targets within the cancer cells with enhanced cell membrane permeability, oral administration, selectivity, and specific affinity. The objective of this review is to highlight the clinical importance and synthetic routes of new small molecule oncology drugs approved by the FDA during the period 2021-2022. These marketed drugs are listed based on the month and year of approval in chronological order. We believed that an in-depth insight into the synthetic approaches for the construction of these chemical entities would enhance the ability to develop new drugs more efficiently.
Assuntos
Antineoplásicos, Aprovação de Drogas, Bibliotecas de Moléculas Pequenas, Humanos, Antineoplásicos/síntese química, Antineoplásicos/farmacologia, Antineoplásicos/química, Bibliotecas de Moléculas Pequenas/química, Bibliotecas de Moléculas Pequenas/síntese química, Bibliotecas de Moléculas Pequenas/farmacologia, Neoplasias/tratamento farmacológico, Estrutura Molecular, Estados Unidos, United States Food and Drug AdministrationRESUMO
BACKGROUND: Tuberculosis (TB) remains a prominent global health challenge, distinguished by substantial occurrences of infection and death. The upsurge of drug-resistant TB strains underscores the urgency to identify novel therapeutic targets and repurpose existing compounds. Rv0295c is a potentially druggable enzyme involved in cell wall biosynthesis and virulence. We evaluated the inhibitory activity of Food and Drug Administration (FDA)-approved compounds against Rv0295c of Mycobacterium tuberculosis, employing molecular docking, ADME evaluation, and dynamics simulations. METHODS: The study screened 1800 FDA-approved compounds and selected the top five compounds with the highest docking scores. Following this, we subjected the initially screened ligands to ADME analysis based on their dock scores. In addition, the compound exhibited the highest binding affinity chosen for molecular dynamics (MD) simulation to investigate the dynamic behavior of the ligand-receptor complex. RESULTS: Dihydroergotamine (CHEMBL1732) exhibited the highest binding affinity (-12.8 kcal/mol) for Rv0295c within this set of compounds. We evaluated the stability and binding modes of the complex over extended simulation trajectories. CONCLUSION: Our in silico analysis demonstrates that FDA-approved drugs can serve as potential Rv0295c inhibitors through repurposing. The combination of molecular docking and MD simulation offers a comprehensive understanding of the interactions between ligands and the protein target, providing valuable guidance for further experimental validation. Identifying Rv0295c inhibitors may contribute to new anti-TB drugs.
Assuntos
Antituberculosos, Simulação de Acoplamento Molecular, Simulação de Dinâmica Molecular, Mycobacterium tuberculosis, United States Food and Drug Administration, Mycobacterium tuberculosis/enzimologia, Mycobacterium tuberculosis/efeitos dos fármacos, Antituberculosos/farmacologia, Antituberculosos/química, Estados Unidos, Sulfotransferases/metabolismo, Sulfotransferases/química, Sulfotransferases/antagonistas & inibidores, Proteínas de Bactérias/química, Proteínas de Bactérias/metabolismo, Aprovação de Drogas, Humanos, Ligantes, Tuberculose/microbiologia, Tuberculose/tratamento farmacológicoAssuntos
Aprovação de Drogas, Imunoterapia, Carcinoma Nasofaríngeo, Neoplasias Nasofaríngeas, United States Food and Drug Administration, Humanos, Estados Unidos, Carcinoma Nasofaríngeo/tratamento farmacológico, Carcinoma Nasofaríngeo/terapia, Imunoterapia/métodos, Neoplasias Nasofaríngeas/tratamento farmacológico, Neoplasias Nasofaríngeas/terapiaRESUMO
Currently, the lengthy time needed to bring new drugs to market or to implement postapproval changes causes multiple problems, such as delaying patients access to new lifesaving or life-enhancing medications and slowing the response to emergencies that require new treatments. However, new technologies are available that can help solve these problems. The January 2023 NIPTE pathfinding workshop on accelerating drug product development and approval included a session in which participants considered the current state of product formulation and process development, barriers to acceleration of the development timeline, and opportunities for overcoming these barriers using new technologies. The authors participated in this workshop, and in this article have shared their perspective of some of the ways forward, including advanced manufacturing techniques and adaptive development. In addition, there is a need for paradigm shifts in regulatory processes, increased pre-competitive collaboration, and a shared strategy among regulators, industry, and academia.
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Aprovação de Drogas, Humanos, Desenvolvimento de Medicamentos/métodos, Indústria Farmacêutica/métodos, Tecnologia Farmacêutica/métodos, Preparações Farmacêuticas/química, Química Farmacêutica/métodos, Composição de Medicamentos/métodosRESUMO
INTRODUCTION: Novel injectables possess applications in both local and systemic therapeutics delivery. The advancement in utilized materials for the construction of complex injectables has tremendously upgraded their safety and efficacy. AREAS COVERED: This review focuses on various strategies to produce novel injectables, including oily dispersions, in situ forming implants, injectable suspensions, microspheres, liposomes, and antibody-drug conjugates. We herein present a detailed description of complex injectable technologies and their related drug formulations permitted for clinical use by the United States Food and Drug Administration (USFDA). The excipients used, their purpose and the challenges faced during manufacturing such formulations have been critically discussed. EXPERT OPINION: Novel injectables can deliver therapeutic agents in a controlled way at the desired site. However, several challenges persist with respect to their genericization. Astronomical costs incurred by innovator companies during product development, complexity of the product itself, supply limitations with respect to raw materials, intricate manufacturing processes, patent evergreening, product life-cycle extensions, relatively few and protracted generic approvals contribute to the exorbitant prices and access crunch. Moreover, regulatory guidance are grossly underdeveloped and significant efforts have to be directed toward development of effective characterization techniques.
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Aprovação de Drogas, Sistemas de Liberação de Medicamentos, Injeções, United States Food and Drug Administration, Humanos, Estados Unidos, Desenvolvimento de Medicamentos, Composição de Medicamentos, Excipientes/química, Preparações Farmacêuticas/administração & dosagem, Animais, Química FarmacêuticaRESUMO
Gene therapy in pediatrics represents a cutting-edge therapeutic strategy for treating a range of genetic disorders that manifest in childhood. Gene therapy involves the modification or correction of a mutated gene or the introduction of a functional gene into a patient's cells. In general, it is implemented through two main modalities namely ex vivo gene therapy and in vivo gene therapy. Currently, a noteworthy array of gene therapy products has received valid market authorization, with several others in various stages of the approval process. Additionally, a multitude of clinical trials are actively underway, underscoring the dynamic progress within this field. Pediatric genetic disorders in the fields of hematology, oncology, vision and hearing loss, immunodeficiencies, neurological, and metabolic disorders are areas for gene therapy interventions. This review provides a comprehensive overview of the evolution and current progress of gene therapy-based treatments in the clinic for pediatric patients. It navigates the historical milestones of gene therapies, currently approved gene therapy products by the U.S. Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) for children, and the promising future for genetic disorders. By providing a thorough compilation of approved gene therapy drugs and published results of completed or ongoing clinical trials, this review serves as a guide for pediatric clinicians to get a quick overview of the situation of clinical studies and approved gene therapy products as of 2023.
Assuntos
Aprovação de Drogas, Terapia Genética, Pediatria, Humanos, Terapia Genética/métodos, Criança, Pediatria/métodos, Doenças Genéticas Inatas/terapia, Doenças Genéticas Inatas/genética, Doenças Genéticas Inatas/tratamento farmacológico, Ensaios Clínicos como AssuntoRESUMO
This Viewpoint examines the appropriateness of FDA accelerated approval of novel gene therapies to treat boys with Duchenne muscular dystrophy following clinical trials with surrogate outcomes that did not demonstrate net benefits.
Assuntos
Terapia Genética, Distrofia Muscular de Duchenne, United States Food and Drug Administration, Distrofia Muscular de Duchenne/terapia, Distrofia Muscular de Duchenne/genética, Humanos, Estados Unidos, Aprovação de Drogas, Distrofina/genéticaRESUMO
With immunotherapy historically focused on cutaneous melanoma, there has been a new wave of systemic medications available for treating non-melanoma skin cancers including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC). The immune checkpoint inhibitors approved by the FDA target programmed cell death protein 1 (PD-1) and the Hedgehog (Hh) signaling pathway. These medications have expanded treatment options; however, side effects are an important consideration. We used the FDA Adverse Events Reporting System (FAERS) to characterize the most prevalent, real-world side effects experienced by patients on these agents. Muscle spasms (23.45%), alopecia (16.06%), ageusia (12.02%), taste disorder (11.91%), and fatigue (11.67%) were the five most common side effects reported with medications used for BCC treatment. Logistic regression analysis showed males on vismodegib for BCC having greater odds of experiencing muscle spasms (aOR 1.33, P<0.001) and ageusia (aOR 1.34, P<0.001) versus females, who were more likely to exhibit alopecia (aOR 1.82, P<0.001) and nausea (aOR 1.96, P<0.001). With SCC treatment, the 5 most reported adverse events were fatigue (5.58%), rash (3.59%), asthenia (3.59%), pruritus (3.19%), and pyrexia (2.79%). Patients taking cemiplimab-rwlc for BCC compared to SCC were more likely to experience disease progression (aOR 10.98, P=0.02). With medication labels providing an excessively daunting list of side effects, we characterize practical side effects seen in patients receiving systemic treatments for non-melanoma skin cancers. J Drugs Dermatol. 2024;23(5):301-305. doi:10.36849/JDD.7968.
