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Rationale and design of the ADAPT-TAVR trial: a randomised comparison of edoxaban and dual antiplatelet therapy for prevention of leaflet thrombosis and cerebral embolisation after transcatheter aortic valve replacement.

INTRODUCTION: Optimal antithrombotic strategy following transcatheter aortic valve replacement (TAVR) is still unknown. We hypothesised that the direct factor Xa inhibitor edoxaban can potentially prevent subclinical leaflet thrombosis and cerebral embolisation compared with conventional dual antiplatelet therapy (DAPT) in patients undergoing TAVR. METHODS AND ANALYSIS: The ADAPT-TAVR trial is an international, multicentre, randomised, open-label, superiority trial comparing edoxaban-based strategy and DAPT strategy in patients without an indication for oral anticoagulation who underwent succ

Identifying and repurposing antiviral drugs against severe acute respiratory syndrome coronavirus 2 with in silico and in vitro approaches.

Coronavirus infectious diseases 2019 (COVID-19), a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a serious public health threat worldwide. So far, there are no drugs and vaccines whose efficacy has been well-proven. After the outbreak, there has been a massive search for anti-SARS-CoV-2 medications, focusing on approved drugs because repurposing approved drugs will take less time to reach clinical usage than new drugs. This article summarizes the studies using in silico and in vitro approaches to identify therapeutic candidates among approved

Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical-Experimental, and Real-World Evidence.

Spinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. The aim of this narrative review was to provide an overview of the pre- and post-marketing evidence on the pharmacological treatments approved for the treatment of SMA by identifying preclinical and clinical studies registered in clinicaltrials.gov and in the EU PAS register from their inception until the 4 January 2023. The preclinical evidence o

Assessment of the availability of repurposed orphan drugs in India.

India has a massive burden of rare diseases (RDs), with an estimated 96 million people living with RDs but limited options for treatment. Repurposing drugs used for other common conditions are essential alternative for RDs due to their cost-effectiveness and reduced timeline. India's patent regime prevents the evergreening of drugs, and a large generic manufacturing industry provides ample opportunity to explore the potential of repurposed drugs for treating RDs, known as repurposed orphan drugs (ROD). However, there is no portal or other source for information on orphan drugs in India. This s

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… However, there is an absence of a dedicated orphan drug approval system or information portal in India. As such, information on the availability of these drugs is difficult to access [ 12 ]. There has been no study to assess the availability of ODs in India. … We identified 279 (27%) small molecule drugs out of 1033 orphan-designated drugs approved by the USFDA till 2021, as repurposed for orphan use, and are out of marketing exclusivity period by 2020. …

Safety assessment of FDA-approved (orlistat and lorcaserin) anti-obesity medications.

INTRODUCTION: Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. AREAS COVERED: This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. EXPERT OPINION: Researc

Evaluation of Pre-marketing Factors to Predict Post-marketing Boxed Warnings and Safety Withdrawals.

INTRODUCTION: An important goal in drug regulation is understanding serious safety issues with new drugs as soon as possible. Achieving this goal requires us to understand whether information provided during the Food and Drug Administration (FDA) drug review can predict serious safety issues that are usually identified after the product is approved. However, research on this topic remains understudied. In this paper, we examine whether any pre-marketing drug characteristics are associated with serious post-marketing safety actions. METHODS: We study this question using an internal FDA databas

Melphalan flufenamide for relapsed/refractory multiple myeloma.

Despite therapeutic advances and improved patient outcomes in recent years, multiple myeloma (MM) remains a mostly incurable hematologic malignancy. Patients with relapsed/refractory MM (RRMM), especially those with triple-class-refractory disease or poor-prognostic features, have substantially unmet needs for new therapies with novel mechanisms of action. Melphalan flufenamide (melflufen) is the first alkylating peptide-drug conjugate that targets aminopeptidases to show efficacy and manageable safety, in combination with dexamethasone, in patients with RRMM who had received at least 4 prior

Structure based virtual screening of the Ebola virus trimeric glycoprotein using consensus scoring.

Ebola virus (EBOV) causes zoonotic viral infection with a potential risk of global spread and a highly fatal effect on humans. Till date, no drug has gotten market approval for the treatment of Ebola virus disease (EVD), and this perhaps allows the use of both experimental and computational approaches in the antiviral drug discovery process. The main target of potential vaccines that are recently undergoing clinical trials is trimeric glycoprotein (GP) of the EBOV and its exact crystal structure was used in this structure based virtual screening study, with the aid of consensus scoring to sele

Changes in Doravirine Pharmacokinetics During Pregnancy: A Longitudinal Single Dose Study.

Physiological changes during pregnancy may alter the pharmacokinetics of antiretrovirals, but pregnancy pharmacokinetic/dynamic data may lag years after drug approval. This single-dose approach allows for earlier data generation, estimating total and protein-unbound doravirine pharmacokinetics in women living with HIV during their second trimester, third trimester, and postpartum.

Pregnancy interruption using mifepristone (RU-486). A new choice for women in the USA.

Mifepristone (RU-486) has recently been granted approval from the Food and Drug Administration for the early termination of pregnancy. Availability is anticipated during 1997. This article describes the pharmacologic function of mifepristone and discusses its potential clinical use in the United States, including its safety, efficacy, and possible complications.

The wobbly status of ketolides: where do we stand?

Ketolides are erythromycin A derivatives with a keto group replacing the cladinose sugar and an aryl-alkyl group attached to the lactone macrocycle. The aryl-alkyl extension broadens its antibacterial spectrum to include all pathogens responsible for community-acquired pneumonia (CAP): Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis as well as atypical pathogens (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila). Ketolides have extensive tissue distribution, favorable pharmacokinetics (oral, once-a-day) and useful anti-inflammatory/immunomodulatory pr

Market withdrawal of new molecular entities approved in the United States from 1980 to 2009.

PURPOSE: Economic factors, market dynamics, and safety issues are largely responsible for decisions to withdraw pharmaceutical products from the market. In this study, new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) were examined in the USA from 1980 to 2009. METHODS: Data were obtained from the FDA, Micromedex, Medline, and Lexis-Nexis. Descriptive analyses were used to classify product discontinuations by therapeutic category, time frame for discontinuation, and reason for withdrawal. RESULTS: There were 740 NMEs approved by the FDA during the study period.

Therapeutic antibiotics in animal feeds and antibiotic resistance.

Recent statutory changes involving animal drugs are expected to facilitate the therapeutic use of antibiotics in animal feeds in the United States of America. The use of antibiotics in animal feeds is controversial due to the potential development of resistant bacterial pathogens in food-producing animals which are exposed to the antibiotics and the resultant public health risk. Zoonotic micro-organisms can be transmitted to humans through contact with animal populations, either directly or through the consumption of contaminated food. Recommendations to address the public health concerns incl

Copper Histidinate: Pediatric First Approval.

Copper histidinate (ZYCUBO®) is a bioavailable copper replacement therapy developed by Cyprium Therapeutics and Sentynl Therapeutics for the treatment of Menkes disease, a genetic disorder caused by variants in the copper transporter gene, ATP7A. Because copper cannot be absorbed from the gastrointestinal tract by individuals with Menkes disease, copper histidinate is administered as a daily subcutaneous injection. In January 2026, copper histidinate received its first approval in the USA by the U.S. Food and Drug Administration for the treatment of Menkes disease in pediatric patients. Orphan

Inebilizumab: First Approval.

Inebilizumab (Uplizna™; inebilizumab-cdon in the USA) is a humanised anti-CD19 monoclonal antibody being developed by Viela Bio for the treatment of a range of autoimmune diseases associated with CD19-expressing B cells. Inebilizumab targets and depletes CD19-expressing B cells through antibody-dependent cell-mediated cytotoxicity. In June 2020, inebilizumab received its first global approval in the USA for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are seropositive for immunoglobulin G autoantibodies against aquaporin-4 (AQP4-IgG). The drug is also u

Ipilimumab-Induced Granulomatous Disease Occurring Simultaneously With Disease Progression in a Patient With Metastatic Melanoma.

Malignant melanoma is the most aggressive cutaneous malignancy with dismal prognosis in the advanced setting. The food and drug administration approval of ipilimumab, the monoclonal antibody against cytotoxic T-lymphocyte antigen 4, has significantly changed treatment strategies for this disease. However, the spectrum of immune-related adverse events secondary to ipilimumab therapy is a growing area of research, and clinical observations of rare immune events as a result of such therapies continue to be reported since the approval. The co-occurrence of disease progression along with an immune-

TB Alliance regimen development for multidrug-resistant tuberculosis.

The recent approval of new tuberculosis (TB) drugs raises hope for new and more effective anti-tuberculosis treatment regimens. The Global Alliance for TB Drug Development (TB Alliance) is committed to ensuring that new anti-tuberculosis drugs fulfill the needs of patients, their families and the local health services that serve the communities. Here we present highlights of the TB Alliance's pipeline of regimen development, with novel regimens for patients with drug-susceptible, multidrug-resistant and extensively drug-resistant TB. The ongoing clinical trials (STAND, NC-005, Nix-TB and LIN-C

Spotlight on ixazomib: potential in the treatment of multiple myeloma.

Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs) such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical prop

Clinical Trials Portfolio and Regulatory History of Idelalisib in Indolent Non-Hodgkin Lymphoma: A Systematic Review and Meta-analysis.

IMPORTANCE: Idelalisib is a first-in-class phosphatidylinositol 3-kinase inhibitor that received US Food and Drug Administration accelerated approval in July 2014 as a single-agent treatment for relapsed follicular lymphoma (FL) and small lymphocytic lymphoma (SLL). Serious adverse effects were reported in 2016 leading to termination of postmarketing registry trials. However, idelalisib remained on the market until 2022 when Gilead voluntarily withdrew the drug for the accelerated approval indication. OBJECTIVE: Evaluate the regulatory oversight of the accelerated approval pathway and evidenc

Characteristics of Youth With Type 2 Diabetes Prescribed Sodium-Glucose Cotransporter-2 Inhibitors Surrounding FDA Approval at an Academic Pediatric Medical Center.

OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were approved by the United States Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus (T2DM) in children aged 10 years and older on June 20, 2023. We describe SGLT2i prescribing trends among all specialties at a quaternary care pediatric medical center surrounding the approval of empagliflozin, then identify characteristics of patients with T2DM associated with a higher likelihood of SGLT2i prescription by pediatric endocrinologists. METHODS: We compared the total number of new SGLT2i prescriptions sen