Remdesivir emergency approvals: a comparison of the U.S., Japanese, and EU systems.

INTRODUCTION: There were no formal regulatory approvals for antivirals for the COVID-19 pandemic as of June 2020. AREAS COVERED: We compare the first regulatory approvals for remdesivir, through emergency pathways available to three of the main regulators in the world, the U.S., Japan, and the EU. We look at the data supporting the decisions and how authorities exchanged information and collaborated to speed up approvals. Based only on topline data available as of 29 April 2020, regulators granted approvals to remdesivir based on very limited but robust data and waiting for more safety and efficacy data. This included the Emergency Use Authorization in the U.S. on 1 May, the Special Approval for Emergency in Japan on 7 May, and Compassionate Use (3 April) followed by a Conditional Marketing Authorization in Europe (Opinion 25th June, Decision (3 July)). EXPERT OPINION: While the regulatory approvals were clearly based on evidence, regulators used agile methods to speed up approval, and make the first antiviral with reliable data available to patients in their constituencies in a very short time frame. More data and wider patient access are still necessary for this product, and more treatments are needed for patients affected by COVID-19.

Medicine safety in pregnancy and ambitions for the EU medicine regulatory framework.

Is the European Union (EU) regulatory framework concerning pregnant women and women at risk of becoming pregnant fit for the purpose? This article discusses improvements in how medicines should be developed and monitored for safe and effective use by pregnant women and women at risk of becoming pregnant.

The development of pharmacological treatment of obesity in children. A European regulatory perspective.

Childhood obesity is recognized by the World Health Organization as one of the most serious public health challenges of the 21st century. Current treatment recommendations consider the role of pharmacotherapy in the treatment of childhood obesity, as an adjunct to lifestyle modifications. This article focuses on key requirements for paediatric development of medicines for obesity in Europe with reference to the European Medicines Agency guideline and a review of Paediatric Investigation Plans (PIP) submitted for this condition, under Regulation (EC) No. 1901/2006 on medicines for paediatric use. To date the European Medicines Agency (EMA) received four paediatric investigation plans for childhood obesity. Issues encountered during the assessment of paediatric investigation plans were all related to the characteristics of the patient population, trial design, choice of endpoints, and safety aspects. Although the number of paediatric investigation plans submitted to the European Medicines Agency thus far is limited, current experience highlights the need for clinical trial protocols that are in line with the specific European guideline. Divergent approaches should be discussed with regulatory authorities before paediatric trials are initiated and included in paediatric investigation plans.

Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options.

Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson-dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies.

Increased PIVKA-II concentrations in patients with cystic fibrosis.

Serum vitamin K concentrations and prothrombin induced by absence of vitamin K (PIVK-II) concentrations were assayed in 43 patients with cystic fibrosis. Twenty nine showed a normal PIVKA-II and vitamin K concentrations; 14 showed an increased PIVKA-II concentration, in one of whom serum vitamin K was decreased. Although their vitamin K concentrations were normal, some patients with cystic fibrosis still had an increased PIVKA-II. There was a significant correlation between PIVKA-II concentrations and the administration of antibiotics, a factor which has not previously been considered responsible for an increase in PIVKA-II.

Testing for course patterns in Crohn's disease using clustering analysis.

Using clustering analysis, we sought to identify groups of patients on the basis of the disease course among a population of 177 patients with Crohn's disease and followed for 3 years or more, starting from the first frank exacerbation of the disease. The first 36 values of a monthly clinical score represented the active variables of the clustering analysis. This method yielded 2 course groups, A and B, of 95 and 82 patients respectively. The unfavorable course in group A was characterized by the persistence of the clinically active disease at 3 years, whereas group B individuals achieved complete clinical remission within 2 years of onset on the average. Among the initially known clinical data which could explain the course, only the incidence of an occlusive syndrome was higher in group B, which showed a more favorable course. Although we applied clustering analysis to a patient sample over a period of only 3 years, our results do suggest the existence or 2 primary course groups within the population of patients with Crohn's disease. It would appear that the disease course cannot be predicted from the clinical parameters present at the time of onset, but rather becomes apparent during the course of the first 2 years.

[Constant flow alimentation in Crohn's disease of children]. / L'alimentation à débit constant au cours de la maladie de Crohn de l'enfant.

Enteral nutrition in children with Crohn's disease is a preferred treatment of acute attacks. When maintained for three months, it effectively acts on digestive symptoms, makes possible the resumption of growth and onset of a delayed puberty. In contrast, it does not appear to modify the long-term course of the disease: 7 out of 10 patients had relapses 3 to 6 months after interruption of enteral nutrition.

[Pharmacokinetics of ceftazidime in cystic fibrosis]. / Pharmacocinétique de la ceftazidime dans la mucoviscidose.

Ceftazidime has been recognized as an invaluable antibiotic for the treatment of lower respiratory infections in patients with cystic fibrosis. In these patients the apparent volume of distribution of ceftazidime is increased. Its clearance is besides increased, with a significant reduction in the area under concentrations curve. The distribution of ceftazidime in the bronchi seems to be very satisfactory. It results from these data that dosage in children with cystic fibrosis may reach 200 to 300 mg/kg/day divided into 3 or 4 injections. The intrabronchial administration of ceftazidime has not proved effective.