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Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection.

Venezuelan equine encephalitis virus (VEEV) is a category B select agent pathogen that can be aerosolized. Infections in murine models and humans can advance to an encephalitic phenotype which may result in long-term neurological complications or death. No specific FDA-approved treatments or vaccines are available for the treatment or prevention of VEEV infection. Neurotropic viral infections have two damaging components: neuronal death caused by viral replication, and damage from the subsequent inflammatory response. Reducing the level of inflammation may lessen neurological tissue damage tha

Twenty-Five Years of Gene Therapy for ADA-SCID: From Bubble Babies to an Approved Drug.

Twenty-five years have passed since first attempts of gene therapy (GT) in children affected by severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) defect, also known by the general public as bubble babies. ADA-SCID is fatal early in life if untreated. Unconditioned hematopoietic stem cell (HSC) transplant from matched sibling donor represents a curative treatment but is available for few patients. Enzyme replacement therapy can be life-saving, but its chronic use has many drawbacks. This review summarizes the history of ADA-SCID GT over the last 25 years, starting from fi

Comparing the Approval and Coverage Decisions of New Oncology Drugs in the United States and Other Selected Countries.

BackgroundGlobal pharmaceutical sales for anticancer drugs were $74.4 billion in 2014, ranking first for drugs by therapeutic class. Countries may differ substantially in the approval and coverage decisions for anticancer drugs.ObjectiveTo compare the approval and coverage decisions for new anticancer drugs between the United States and 4 other countries: the United Kingdom, France, Australia, and Canada.MethodsWe identified all new anticancer drug indications approved by the FDA between January 1, 2009, and December 31, 2013. For each country, we reviewed the organizations, processes, criteri

Approved oncology drugs lack in vivo activity against Trichuris muris despite in vitro activity.

Infections with soil-transmitted helminths (STHs) are considered among the most persistent global health problems. The few available drugs have limitations including low efficacy against Trichuris trichiura infections. As a starting point toward drug repositioning, we studied a set of FDA-approved oncology drugs for activity against Trichuris muris since targets relevant to cancer therapy might have a function in helminth biology. Drugs were tested in vitro on the larval and adult stage of T. muris. Compounds active in vitro were tested in the T. muris mouse model at single oral dosages of 200

Homoharringtonine, a clinically approved anti-leukemia drug, sensitizes tumor cells for TRAIL-induced necroptosis.

BACKGROUND: One hallmark of cancer cells is their ability to evade physiologic signals causing regulated cell death (RCD). Correspondingly, TRAIL-based therapies to eliminate human cancer cells via enforced induction of apoptosis have been established and represent a promising approach in anti-cancer research. However, due to frequently appearing intrinsic or acquired resistances of tumor cells against apoptosis, TRAIL-based apoptotic strategies for the treatment of cancer patients have shown limited efficacy. As a potential alternative, regulated necrosis (and necroptosis triggered e.g. by TR

Telavancin: the long and winding road from discovery to food and drug administration approvals and future directions.

Telavancin (TD-6424) was discovered in 2000 and became the first marketed semisynthetic lipoglycopeptide in 2009. This parenteral antibacterial agent has a dual mechanism of action and potent in vitro activity against gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and isolates with reduced vancomycin susceptibility. Pharmacokinetic and pharmacodynamic analyses support the concentration-dependent activity and once-daily dosing regimen of telavancin. A changing regulatory approval process, manufacturing obstacles, and the termination of a commercialization partner

Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library.

Although antibiotic treatment for Lyme disease is effective in the majority of cases, especially during the early phase of the disease, a minority of patients suffer from post-treatment Lyme disease syndrome (PTLDS). It is unclear what mechanisms drive this problem, and although slow or ineffective killing of Borrelia burgdorferi has been suggested as an explanation, there is a lack of evidence that viable organisms are present in PTLDS. Although not a clinical surrogate, insight may be gained by examining stationary-phase in vitro Borrelia burgdorferi persisters that survive treatment with th

Supplemental applications proposing labeling changes for approved drugs, biologics, and medical devices. Final rule.

The Food and Drug Administration (FDA) is amending its regulations regarding changes to an approved new drug application (NDA), biologics license application (BLA), or medical device premarket approval application (PMA). This final rule provides that a supplemental application submitted under certain FDA regulations is appropriate to amend the labeling for an approved product to reflect newly acquired information and to add or strengthen a contraindication, warning, precaution, or adverse reaction if there is sufficient evidence of a causal association with the drug, biologic, or device, as de

Comparison of novel oncology drugs that received dual approval from the US accelerated approval and EU conditional marketing authorisation pathways, 2006-2021: a cross-sectional study.

ObjectiveWe aimed to provide insight into differences in drug review decisions made by the US Food and Drug Administration's (FDA) accelerated approval (AA) pathway and the European Medicines Agency's (EMA) conditional marketing authorisation (CMA) pathway, and to add to the current knowledge base of drug approval processes.Design, setting, participantsThis cross-sectional study thoroughly examines novel oncology drugs with dual approval through FDA AA and EMA CMA between 2006 and 2021. Statistical analysis was performed from June to July 2022.Primary and secondary outcome measuresThe study ex…

Therapeutic efficacy and safety of newly approved FDA drug levoketoconazole in cushing syndrome: a systematic review.

BACKGROUND: Cushing syndrome is a severe endocrinopathy due to chronic hypercortisolism with etiology that includes the administration of exogenous glucocorticoids, pituitary adenomas, ectopic ACTH-producing tumors, and adrenal tumors. Expressed as central obesity, hypertension, glucose intolerance, and psychiatric symptoms, it greatly affects the QoL and has a high association with morbidity and mortality. AIM: This systematic review summarizes data from clinical trials to compare the effectiveness and safety of a newly approved drug, levoketoconazole, for the treatment of Cushing syndrome.

New small molecular drug approvals for 2025: clinical applications, mechanism of action, and chemical synthesis.

In 2025, the U.S. FDA approved 46 new drug applications, including 34 new molecular entities and 12 biologics license applications. The new molecular entities include 31 small-molecule drugs and 3 oligonucleotides, while the biological license applications cover monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, and fusion proteins. These newly approved molecules not only feature favorable skeletal structures but also embody the comprehensive achievements of multiple fields, including modern drug discovery, drug synthesis, and the study of pathogenesis. In this review, we

Post-Marketing Requirements for Anticancer Drugs Approved in Japan, 2001-2024: A Cross-Sectional Analysis.

The accelerated development of innovative anticancer therapies has led to the early approval of an increasing number of drugs. However, clinical evidence available at the time of approval is often limited, necessitating additional post-marketing studies to supplement safety and efficacy data. Therefore, post-marketing requirements (PMRs) have gained greater regulatory importance. Nevertheless, the current landscape of PMRs for anticancer drugs in Japan has not been clearly characterized. In this study, we aimed to characterize the status, content, and trends of PMRs for anticancer drugs approv

Closantel, an FDA-approved veterinary drug, suppresses PEDV replication via targeting main protease.

Porcine epidemic diarrhea virus (PEDV) continues to pose a global threat to the swine industry, causing fatal neonatal diarrhea with a mortality rate approaching 100%. Currently, no effective targeted drugs have been approved. The coronavirus main protease (Mpro), a conserved enzyme essential for viral replication, represents a promising target for antiviral development. Here, we demonstrate that Closantel, an FDA-approved veterinary drug, acts as a potent pan-coronavirus Mpro inhibitor via enzymatic inhibition assays. Moreover, Closantel potently suppresses PEDV replication in Vero-E6 and IPE

The Role of Pyrrolidine in Antibacterial Drug Discovery: Clinically Approved Antibiotics, Novel Derivatives, and Future Perspectives.

Antimicrobial resistance is a major global health challenge that has created an urgent need for new antibacterial agents capable of overcoming emerging resistance mechanisms. Among nitrogen-containing heterocycles, pyrrolidine has been widely investigated in medicinal chemistry due to its structural versatility, favourable physicochemical properties, and ability to enhance interactions with biological targets. This review provides a comprehensive and critical overview of pyrrolidine-based compounds investigated for antibacterial applications. Relevant studies describing clinically approved ant

Pediatric Extrapolation in Neuropsychiatric Drug Development: Leveraging Pharmacokinetic and Pharmacodynamic Strategies to Facilitate FDA Approvals.

Pediatric extrapolation enables the application of adult efficacy data to pediatric populations when sufficient similarity is established in disease pathophysiology, pharmacologic response, and drug exposure. When these conditions are met, extrapolation can reduce or eliminate the need for dedicated pediatric efficacy trials, facilitating more efficient pediatric drug development. In this paper, we examined US Food and Drug Administration (FDA) pediatric drug approvals in neurology, analgesia, and psychiatry from 2014 to 2025 that utilized exposure matching to support extrapolation approaches.…

Infectious Complications of Antibody-Drug Conjugates: A Review of Safety Data from FDA-Approved Agents.

PURPOSE OF REVIEW: With fifteen agents now FDA-approved and indications expanding into earlier treatment lines, antibody-drug conjugates (ADCs) represent a rapidly growing class of targeted cancer therapeutics. Despite their selective mechanism of action, infectious complications are clinically significant and have been flagged as a disproportionate safety signal in post-marketing surveillance. This review characterizes the infection risk profiles of all fifteen FDA-approved ADCs through systematic extraction of prescribing information and pivotal trial safety data, and examines the pathophysi

Совпадение в полном тексте источника
… Primary data were obtained from the FDA Drugs@FDA database [ 14 ], which provides comprehensive access to drug approval packages, prescribing information, and safety updates. …

Pharmacological aspects of FDA-approved novel drug therapies against cancer in 2023: a comprehensive review.

This manuscript is aimed at preparing a scientific report on anticancer drugs, covering pharmacological aspects, approved by the FDA in the year 2023. This article is anticipated to serve as a handy document of interest for oncologists, patients as well as academicians. The manuscript was prepared by studying the pre-clinical and clinical data available in the public domain specifically on the website of the USFDA, Clinical Trials, National Library of Medicine, and other sources. The FDA reports were comprehensively reviewed where specific information on drug approvals, safety evaluations, pha…

Excipients in drug delivery systems: A comprehensive review of approved inactive ingredients for human ophthalmic formulations.

Pharmaceutical excipients, commonly known as inactive ingredients, encompass any substance aside from the active ingredient that fulfills a distinct and vital role in a formulation. Their purpose is to enhance specific characteristics, whether associated with the performance of the formulation or aspects related to patient comfort, safety, and acceptability. Because of the limited toxicity studies provided, and the several allergic and toxic side effects that have been reported throughout the years, it is not trivial for the regulatory agencies to approve inactive ingredients for human use. In

The Impact of Survival Benefit and Study Design on FDA Approval for Anticancer Drugs Over the Past Decades.

Despite the tremendous effort in the oncology community, the success rate of anticancer development remained low at 30% to 40% from the Phase 3 study to the regulatory approval. The factors associated with the regulatory approval for market authorization have gained interest in the community to improve the success rate of drug development. Using the data from 208 Phase 3 studies for anticancer drugs, we explored the possible factors associated with the US Food and Drug Administration's (FDA's) approval by multivariate logistic regression analysis. The model incorporated 21 factors from therape

Совпадение в полном тексте источника
… Prediction of drug approval after phase I clinical trials in oncology: RESOLVED2. JCO Clin Cancer Inform. 2019;3:1‐10. 12. US Food and Drug Administration . Benefit‐risk assessment for new drug and biological products guidance for industry. 2023. …

The Evaluation of Interactions Between Multiple Intrinsic and Extrinsic Factors Reported in Labeling for FDA-Approved Drugs.

A critical aspect of drug development is evaluating pharmacokinetics (PK) and pharmacodynamics to assess how intrinsic (e.g., age, sex, comorbidities, and genomics) and extrinsic (e.g., drug-drug interactions [DDIs] and food interaction) factors influence drug exposure and response. These aspects guide dose selection and inform drug labeling by accounting for interindividual variability to ensure safe and effective use across complex patient populations. However, identifying the relationship of co-occurring factors, resembling complex patient populations, remains challenging. Herein, we analyz