Considerations and Challenges in the Remdesivir COVID-19 Pediatric Development Program.

The US Food and Drug Administration is committed to the development of effective antiviral regimens for pediatric patients with coronavirus disease 2019 (COVID-19), including infants and neonates. On April 25, 2022, the approved indication of remdesivir (RDV) was expanded to include pediatric patients 28 days and older and weighing at least 3 kg with positive results of direct severe acute respiratory syndrome coronavirus 2 viral testing, who are: Hospitalized, or Not hospitalized and have mild to moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death. Given the similar course of COVID-19 in adults and pediatric patients, the approval of RDV for use in pediatric patients is supported by the safety and efficacy data from adequate and well-controlled phase 3 trials in adults and adolescents; and by the safety and pharmacokinetic data from a single-arm, open-label, phase 2/3 pediatric clinical trial of 53 pediatric patients at least 28 days of age and weighing at least 3 kg with confirmed severe acute respiratory syndrome coronavirus 2 infection and mild, moderate, or severe COVID-19.

Benefit-risk assessment for brincidofovir for the treatment of smallpox: U.S. Food and Drug Administration's Evaluation.

The development and approval of brincidofovir for the treatment of smallpox, a disease that was eradicated from the world over 40 years ago, has resulted in the second antiviral approved via the Medical Countermeasure Initiative (MCMi) to combat this disease. Approval of brincidofovir required a unique regulatory approach based on the FDA Animal Rule, and development was supported by many years of research and collaboration among academic investigators, the pharmaceutical industry and multiple government agencies. This article summarizes the FDA regulatory pathway and describes the challenges involved.

Sustained virological response rates with direct-acting antivirals in black subjects with HCV genotype 1 infection: systematic analysis of clinical trials.

Objectives: Under representation of black subjects in trials of hepatitis C virus (HCV) direct-acting antivirals (DAAs) complicates assessment of differential outcomes for black individuals non-black individuals. HCV trials submitted to the Food and Drug Administration (2013-2017) to support approval or to expand an indication of 12-week interferon-free DAA regimens with or without ribavirin to treat HCV genotype 1 (GT1) infection were pooled to explore efficacy comparisons by ethnicity.

Methods: Twenty-six trials were pooled and included 2869 individuals with HCV GT1 alone and 742 individuals with both HCV GT1 and HIV.

Benefit-risk assessment for sofosbuvir/velpatasvir/voxilaprevir based on patient population and hepatitis C virus genotype: U. S. Food and Drug Administration's evaluation.

On July 18, 2017, the U.S. Food and Drug Administration (FDA) approved sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) fixed-dose combination (FDC), an interferon-free, complete regimen for adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have: • genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing a nonstructural protein 5A (NS5A) inhibitor; and • genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.

How Often Are Drugs Made Available Under the Food and Drug Administration's Expanded Access Process Approved?

In this review of individual patient expanded-access requests to the Center for Drug Evaluation and Research for the period Fiscal Year 2010 to Fiscal Year 2014, we evaluated the number of applications received and the number allowed to proceed. We also evaluated whether drugs and certain biologics obtained under expanded access went on to be approved by the Food and Drug Administration. Finally, we considered concerns that adverse events occurring during expanded access might place sponsors at risk for legal liability.

Clinical experience with intravenous zanamivir under an Emergency IND program in the United States (2011-2014).

Background: Since the emergence of 2009 H1N1 virus, intravenous (IV) zanamivir has been authorized as an investigational treatment for patients with serious and life-threatening influenza through an Emergency Investigational New Drug application (EIND). This review encompasses the FDA's EIND database from May 2011 to June 2014.

Methods: This is a retrospective descriptive review of patient clinical data in the FDA's IV zanamivir EIND database from May 2011 to June 2014.

Why did the FDA approve efavirenz 800 mg when co-administered with rifampin?

Objectives: Literature reports regarding the efficacy of efavirenz (EFV) 600 mg with rifampin (RIF) are not consistent. Evaluation of a drug-drug interaction (DDI) study and supportive semi-mechanistic population pharmacokinetic (PK) analyses were undertaken to help delineate this issue.

Design/methods: DDI study and supportive semi-mechanistic population PK analyses were provided by BMS.

Original research: Intravenous ribavirin--review of the FDA's Emergency Investigational New Drug Database (1997-2008) and literature review.

Intravenous (IV) ribavirin does not have US Food and Drug Administration (FDA) approval, although oral and aerosol formulations have been approved. Intravenous ribavirin can, however, be authorized for use as a result of an Emergency Investigational New Drug (EIND) application as investigational treatment for patients with serious viral infections, including emerging or rare infections for which no alternative treatment is available. This retrospective study evaluated clinical experience with IV ribavirin based on a review of the FDA's EIND database and a literature review.

Regulatory issues in developing new HIV protease inhibitors: risks and benefits.

Purpose Of Review: To provide a regulatory perspective on developing new HIV protease inhibitors. The present review highlights the risks and benefits of certain design aspects for studies in treatment-naïve and treatment-experienced patients, including timing of studies, study design options, choice of control arms, and duration of treatment.

Recent Findings: The present review highlights published studies to illustrate the need for new therapies and highlights potential historical data to help design future HIV clinical trials better.

Risk factors for mortality from primary cryptococcosis in patients with HIV.

Cryptococcosis continues to have a high mortality rate in human immunodeficiency virus (HIV)-positive patients despite advances made in antifungal treatment, intracranial pressure management, and antiretroviral therapy. This retrospective chart review was conducted at the University of Maryland Medical Center and Baltimore VA Medical Center from 1993 to 2004. We reviewed all inpatient cases of cryptococcal infections to assess predictors of inpatient mortality among HIV-positive patients.

Intracranial hemorrhage and liver-associated deaths associated with tipranavir/ritonavir: review of cases from the FDA's Adverse Event Reporting System.

Tipranavir (TPV), a protease inhibitor, has box warnings for intracranial hemorrhage (ICH) and hepatotoxicity (including hepatic failure and death). A box warning is a labeling statement about serious adverse events leading to significant injury and/or death. A box warning is the most serious warning placed in the labeling of a prescription medication.

Are literature references sufficient for dose recommendations? An FDA case study of efavirenz and rifampin.

One of the numerous regulatory functions of the Food and Drug Administration (FDA) is the evaluation of drug-drug interactions and the determination of appropriate dose adjustments, if necessary, to ensure the safe and effective use of medications. The FDA considers several data sources when determining the significance of drug-drug interactions. The majority of dose adjustment recommendations are based on specific drug-drug interactions studies.

Atazanavir-associated nephrolithiasis: cases from the US Food and Drug Administration's Adverse Event Reporting System.

The risk of nephrolithiasis associated with atazanavir is not well characterized. The US Food and Drug Administration's Adverse Event Reporting System was searched for reports of nephrolithiasis in HIV-infected patients taking an atazanavir-based regimen. Thirty cases were identified.

Immune reconstitution inflammatory syndrome presenting as sinusitis with inflammatory pseudotumor in an HIV-infected patient: a case report and review of the literature.

Immune reconstitution inflammatory syndrome (IRIS) encompasses a variety of conditions that occur among HIV-infected patients in a temporal relationship with increases in CD4 cell count as a result of highly active antiretroviral therapy (HAART). Most conditions associated with IRIS are infectious. Malignancies, such as Kaposi's sarcoma, have also been reported.