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Human cytomegalovirus (CMV) susceptibility to currently approved antiviral drugs does not impact on CMV terminase complex polymorphism.

Currently approved anti-human cytomegalovirus (CMV) drugs, all targeting the viral DNA polymerase, are associated with significant toxicities and emergence of drug resistance. In this context, CMV terminase complex constitutes a promising target for novel antiviral compounds. In this study, we describe the low natural polymorphism (interstrain identity >97.7% at both nucleotide and amino acid levels) of the terminase subunits pUL56 and pUL89, and the portal protein pUL104, among 63 CMV clinical strains, and we show that the CMV resistance profile to current DNA polymerase inhibitors has no imp

Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs.

In light of the current outbreak of Ebola virus disease, there is an urgent need to develop effective therapeutics to treat Ebola infection, and drug repurposing screening is a potentially rapid approach for identifying such therapeutics. We developed a biosafety level 2 (BSL-2) 1536-well plate assay to screen for entry inhibitors of Ebola virus-like particles (VLPs) containing the glycoprotein (GP) and the matrix VP40 protein fused to a beta-lactamase reporter protein and applied this assay for a rapid drug repurposing screen of Food and Drug Administration (FDA)-approved drugs. We report her

Comparison of treatment effects between ACR response criteria and target-based outcomes for contemporary rheumatoid arthritis drug approval trials: A meta-epidemiological study.

OBJECTIVE: Regulatory priorities diverge between agencies - the FDA maintained ACR20 response as primary endpoint in rheumatoid arthritis (RA) trials, whereas the EMA emphasized target-based outcomes. We aim to systematically compare treatment effect estimates between American College of Rheumatology (ACR) response criteria (ACR20/50/70) and target-based outcomes in placebo-controlled trials of approved RA therapies. METHODS: A meta-epidemiological study was performed on randomized placebo-controlled trials investigating approved biological and targeted DMARDs (bioDMARDs and tsDMARDs) in pati

How improvements in US FDA regulatory process and procedures led to the drug approval for first ever treatment of a common liver disease.

Metabolic-associated liver disease is a growing public health crisis, with phenotypes from fatty liver to steatohepatitis, previously known … D&C Act) upon which FDA regulation is based, have provided new agency tools that facilitated such a drug approval to address the profound unmet medical need for patients with this metabolic-based liver disease. There is reason for hope that continued evolution of the regulatory process will lead to additional drug approvals, as well as the ability for clinical …

Insights Into Vepdegestrant (ARV-471): The First-in-Class Estrogen Receptor Proteolysis-Targeting Chimera Approaching Food and Drug Administration Approval for Breast Cancer.

Vepdegestrant (ARV-471) is an orally bioavailable, proteolysis-targeting chimera (PROTAC)-based estrogen receptor (ER) degrader and is among the most clinically advanced ER-targeting PROTAC degraders, identified through a rational medicinal chemistry optimization campaign. It is being developed as an oral small-molecule endocrine therapy for advanced or metastatic ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, with particular relevance for tumors harboring ESR1 mutations. On June 6, 2025, Arvinas and Pfizer submitted a New Drug Application (NDA) for vepdeg

US Food and Drug Administration Approval Summary: Imetelstat for Selected Patients With Low- to Intermediate-1 Risk Myelodysplastic Syndromes With Transfusion-Dependent Anemia.

On June 6, 2024, the US Food and Drug Administration (FDA) approved imetelstat (RYTELO, Geron) for adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring ≥4 red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents. The approval was based on a randomized (2:1), double-blind, placebo-controlled multicenter trial, Study MDS3001. In the protocol-specified primary analysis, the ≥8-week RBC transfusion independence (RBC-TI) rate was 39.8% (95% CI, 30.9 to 4

Multifocal and Extended Depth of Focus Intraocular Lenses: A Comparison of Data from the United States Food and Drug Administration Premarket Approval Trials.

PURPOSE: To review and compare the results of unpublished premarket approval studies for recent multifocal and extended depth of focus (EDOF) intraocular lenses. METHODS: Lenses without previously published pre-market approval trials were identified and clinical and patient-reported outcomes were reviewed and compared. RESULTS: Lenses included the DFT/DAT (Acrysof Vivity) EDOF lens, the TFNT/TFAT (PanOptix) trifocal lens, and the SV25T (ReStor ActiveFocus) lens (all from Alcon Laboratories, Inc), as well as the ZXR/ZXT (Tecnis Symfony and Symfony Toric), the ZLB00 (Tecnis Multifocal +3.25),

First Approval of Improved Medical Device Conditional on Use-Result Survey in Japan　- Regulatory Review of Polymer-Free Drug-Coated BioFreedom Coronary Stent.

A prospective randomized clinical trial showed that the BioFreedom stent (Biosensors International), which is a polymer-free and carrier-free drug-coated stent, was significantly superior to a bare-metal stent (BMS) in patients at high bleeding risk who were receiving a 1-month course of dual antiplatelet therapy (DAPT). However, the stent thrombosis rate (2.01% for BioFreedom vs. 2.20% for BMS) was 4-6-fold higher than that of approved drug-eluting stents based on real-world data in Japan. Furthermore, the frequency of stent thrombosis at more than 1 month with the BioFreedom stent was slight

Real-world data in drug development strategies for orphan drugs: Tafasitamab in B-cell lymphoma, a case study for an approval based on a single-arm combination trial.

Tafasitamab (TAF) plus lenalidomide (LEN) is a novel treatment option for patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) who are not eligible for autologous stem cell transplantation. The initial US/EU approvals for TAF represent precedents because this is the first time that approval of a novel combination therapy was granted based on a pivotal single-arm trial (SAT). Matching real-world data (RWD) helped to disentangle the contribution of individual agents. In this review, we present the TAF development strategy, the prospective incorporation of RWD within the clin

Costs and benefits of early access to new cancer drugs through the US Food and Drug Administration's accelerated approval pathway: retrospective observational study and economic evaluation.

OBJECTIVE: To evaluate the survival gains and additional Medicare spending associated with early access to new cancer drugs granted accelerated approval by the US Food and Drug Administration (FDA), compared with access to cancer drugs following completion of confirmatory trials. DESIGN: Retrospective observational study and economic evaluation. SETTING: US Medicare programme, which provides health insurance for adults aged 65 years and older. PARTICIPANTS: Medicare beneficiaries who received new cancer drug indications from the time of FDA accelerated approval to conversion to regular appr

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… The Trade-off Between Speed and Safety in Drug Approvals. JAMA Oncol. 2017;3:1465–6. doi: 10.1001/jamaoncol.2016.3337. 60. … Quality of Life, Overall Survival, and Costs of Cancer Drugs Approved Based on Surrogate Endpoints. JAMA Intern Med. 2017;177:276–7. doi: 10.1001/jamainternmed.2016.7761. 90. Gloy V, Schmitt AM, Düblin P, et al. …

When coverage is not access: A heart transplant recipient's perspective on everolimus, U.S. Food and Drug Administration labeling, and the problem of "ghost approval".

Access to immunosuppressive therapy is essential for long-term survival in heart transplant recipients, yet insurance coverage does not always translate into meaningful access. This perspective introduces the concept of "ghost approval," in which a medication is technically approved but remains financially or logistically inaccessible to the patient. Drawing on a first-person experience with everolimus, an mechanistic target of rapamycin inhibitor without a U.S. Food and Drug Administration indication for heart transplantation, this article highlights the gap between regulatory labeling, clini

Comparison of Drug Use Between Clinical Practice and Regulatory Approval: Results in Older Japanese Patients With Rheumatoid Arthritis, Diabetes, High Blood Pressure, or Depression.

BACKGROUND: In this study, differences in older patients between drug use as reported in clinical practice and in clinical trials for regulatory approval were examined. METHODS: Electronic medical record (EMR) data such as patient background (age, sex), concomitant drugs, data on laboratory tests, and prescribed doses of drugs from outpatients with rheumatoid arthritis, diabetes, high blood pressure, or depression at Chiba University Hospital were obtained for the period from January 2003 to December 2012. These data were compared with data from relevant clinical trials for regulatory approva

FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer.

On October 11, 2006, the U.S. Food and Drug Administration granted approval for bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), administered in combination with carboplatin and paclitaxel, for the initial treatment of patients with unresectable, locally advanced, recurrent, or metastatic, nonsquamous, non-small cell lung cancer (NSCLC). Approval is based on a significant improvement in overall survival (OS). A randomized, open label, multicenter clinical trial, conducted by the Eastern Cooperative Oncology Group (ECOG), in chemotherapy-naïve patients with stage IIIB/IV nonsqua

Evidence supporting European Medicines Agency drug approvals (2020-2023): A cross-sectional study of trial design and outcomes.

BACKGROUND: The strength and transparency of clinical trial evidence supporting drug approvals have become increasingly scrutinized, particularly considering the increased use of regulatory flexibility and expedited pathways. While US Food and Drug Administration standards have been extensively analyzed, evidence standards at the European Medicines Agency remain less well-characterized. Thus, this study aims to systematically assess the design, quality, and outcomes of pivotal efficacy trials supporting European Medicines Agency drug approvals for new active substances between 2020 and 2023. …

Repurposing FDA-approved drugs as multi-target neuroprotective agents for Alzheimer's disease via computational screening and experimental validation.

β-site APP-cleaving enzyme 1 (BACE1, a β-secretase) is a key aspartyl protease that initiates the proteolytic processing of the amyloid precursor protein (APP) to form the amyloid-β (Aβ) peptide. Given that Aβ aggregation and plaque formation are a central pathological feature of Alzheimer’s disease (AD), BACE1 remains a critical therapeutic target. Furthermore, the complexity of AD pathology necessitates the identification of novel multi-target agents. This study employed a structure-based virtual screening, targeting the BACE1 approach to identify the potential BACE1 inhibitors from FDA-appr

Structure-based design of the approved drug zafirlukast identifies HLC40 as a potent WDR5 WIN-site inhibitor with antitumor efficacy.

WD40 repeat-containing protein 5 (WDR5) plays a critical role in chromatin-related processes, and its overexpression is associated with poor prognosis in multiple cancers, making it an attractive therapeutic target. Screening of an approved drug library identified zafirlukast (ZAF), an anti-asthmatic agent, as a binder to the WIN site of WDR5, inhibiting the histone methyltransferase activity of the MLL1 complex with an IC50 of 22.96 μM. Structure-based optimization yielded the candidate HLC40, which not only abolished its original CysLT1 receptor antagonism (IC50 > 5 μM) but also exhibited a

FDA-Approved Drug Repurposing as p53 Mutants Rescue Candidates Using Structure-Based Virtual Screening and Molecular Simulations.

The restoration of mutant p53 stability is a highly sought-after strategy in targeted cancer therapy. This study presents a structure-based virtual screening and molecular dynamics approach to nominate FDA-approved drugs as candidate stabilizers of mutant p53 for downstream experimental validation. A virtual screening library of FDA-approved compounds was docked against three representative p53 mutants (7DHY, 7DHZ, and 7V97) to evaluate their binding potential. The prioritized candidates demonstrated consistent, multi-conformer binding affinities. Protein-ligand interaction profiling revealed

Inhibition of efflux pumps by FDA-approved drugs oxiconazole and sertaconazole restores antibiotic susceptibility in multidrug-resistant S. aureus.

Antibiotic resistance in Staphylococcus aureus causes major concern worldwide. In S. aureus, efflux pumps are mostly responsible for the development of multidrug resistance. Active removal of antibiotics from cells by S. aureus efflux pumps, including NorA, NorB, AbcA, and MepA, helps to lower their intracellular concentration and effectiveness. The present study examined two FDA-approved antifungal medications, oxiconazole and sertaconazole, as possible efflux pump inhibitors (EPIs) against multidrug-resistant S. aureus. Our results showed that both drugs reduced the efflux pump activity of d