Entity

Time filter

Source Type

Uppsala, Sweden

Pignatti F.,European Medicines Agency | Ashby D.,Imperial College London | Brass E.P.,University of California at Los Angeles | Eichler H.-G.,European Medicines Agency | And 14 more authors.
Clinical Pharmacology and Therapeutics | Year: 2015

Structured frameworks for benefit-risk analysis in drug licensing decisions are being implemented across a number of regulatory agencies worldwide. The aim of these frameworks is to aid the analysis and communication of the benefit-risk assessment throughout the development, evaluation, and supervision of medicines. In this review, authors from regulatory agencies, pharmaceutical companies, and academia share their views on the different frameworks and discuss future directions. © 2015 American Society for Clinical Pharmacology and Therapeutics.


Gravanis I.,European Medicines Agency | Sancho Lopez A.,Hospital Universitario Puerta Of Hierro | Hemmings R.J.,Medicines and Healthcare Products Regulatory Agency | Camarero Jimenez J.,Agencia Espanola de Medicamentos y Productos Sanitarios | And 7 more authors.
Oncologist | Year: 2013

On September 5, 2011, abiraterone was approved in the European Union in combination with prednisone or prednisolone for the treatment of metastatic castration-resistant prostate cancer (CRPC) in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen. On December 18, 2012, the therapeutic indication was extended to include the use of abiraterone in combination with prednisone or prednisolone for the treatment of metastatic CRPC in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. Abiraterone is a selective, irreversible inhibitor of cytochrome P450 17α, an enzyme that is key in the production of androgens. Inhibition of androgen biosynthesis deprives prostate cancer cells from important signals for growth, even in cases of resistance to castration. At the time of European Union approval and in a phase III trial in CRPC patients who had failed at least one docetaxel-based chemotherapy regimen, median overall survival for patients treated with abiraterone was 14.8 months versus 10.9 months for those receiving placebo (hazard ratio, 0.65; 95% confidence interval 0.54 - 0.77; p<.0001). In a subsequent phase III trial in a similar but chemotherapy-naïve patient population, median radiographic progression-free survival was 16.5 months for patients in the abiraterone treatment arm versus 8.3 months for patients in the placebo arm (hazard ratio, 0.53; 95% confidence interval, 0.45-0.62; p<.0001). Abiraterone was most commonly associated with adverse reactions resulting from increased or excessive mineralocorticoid activity. These were generally manageable with basic medical interventions. The most common side effects (affecting more than 10% of patients) were urinary tract infection, hypokalemia, hypertension, and peripheral edema. © AlphaMed Press 2013.


Pignatti F.,The European Medicines Agency | Ashby D.,Imperial College London | Brass E.P.,University of California at Los Angeles | Eichler H.-G.,The European Medicines Agency | And 14 more authors.
Clinical pharmacology and therapeutics | Year: 2015

Structured frameworks for benefit-risk analysis in drug licensing decisions are being implemented across a number of regulatory agencies worldwide. The aim of these frameworks is to aid the analysis and communication of the benefit-risk assessment throughout the development, evaluation, and supervision of medicines. In this review, authors from regulatory agencies, pharmaceutical companies, and academia share their views on the different frameworks and discuss future directions. © 2015 American Society for Clinical Pharmacology and Therapeutics.


Pignatti F.,European Medicines Agency EMA | Jonsson B.,Lakemedelsverket | Blumenthal G.,U.S. Food and Drug Administration | Justice R.,U.S. Food and Drug Administration
Molecular Oncology | Year: 2015

Drug licensing and approval decisions involve the balancing of benefits against the risks (harms) in the presence of uncertainty. Typically, the benefits are estimated from primary efficacy endpoints from confirmatory (phase III) clinical trials although exceptions where promising early data from single-arm studies have led to accelerated approvals are not uncommon, particularly for cancer drugs.The challenge for regulators is to balance early evidence of efficacy that might support approval versus the need to establish clinical benefit based on conclusive evidence. Targeted agents offer the promise that knowledge about the mechanism of the disease will help identify patients with tumors likely to respond, resulting in higher efficacy and less toxicity, and earlier regulatory decisions based on convincing evidence of clinical benefit.In this paper, we describe methods and examples of benefit-risk assessment of targeted drugs, recent initiatives from EMA and FDA on improving communication about benefits and risks, and discuss future steps. © 2014.


Van Duijkeren E.,National Institute for Public Health and the Environment | Greko C.,National Veterinary Institute | Pringle M.,National Veterinary Institute | Baptiste K.E.,Danish Health and Medicines Authority | And 12 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2014

Pleuromutilins (tiamulin and valnemulin) are antimicrobial agents that are used mainly in veterinary medicine, especially for swine and to a lesser extent for poultry and rabbits. In pigs, tiamulin and valnemulin are used to treat swine dysentery, spirochaete-associated diarrhoea, porcine proliferative enteropathy, enzootic pneumonia and other infections where Mycoplasma is involved. There are concerns about the reported increases in the MICs of tiamulin and valnemulin for porcine Brachyspira hyodysenteriae isolates from different European countries, as only a limited number of antimicrobials are available for the treatment of swine dysentery where resistance to these antimicrobials is already common and widespread. The loss of pleuromutilins as effective tools to treat swine dysentery because of further increases in resistance or as a consequence of restrictions would present a considerable threat to pig health, welfare and productivity. In humans, only one product containing pleuromutilins (retapamulin) is authorized currently for topical use; however, products for oral and intravenous administration to humans with serious multidrug-resistant skin infections and respiratory infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA), are being developed. The objective of this review is to summarize the current knowledge on the usage of pleuromutilins, resistance development and the potential impact of this resistance on animal and human health. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Discover hidden collaborations