Abstract:
PURPOSE:To review the marketing authorization of biosimilars and provide a critical analysis of the pivotal trials supporting their approval by the European Medicines Agency (EMA). METHODS:EMA website to identify the biosimilars approved up to July 2019 and the European Public Assessment Report for information on pivotal trial design, duration, intervention and control, primary outcome, data on immunogenicity, and comparability margins. RESULTS:The EMA has approved 55 biosimilars (62% in 2017-2019) of 16 biologic products, used in several clinical indications. Some biosimilars were licensed as multiple products, with different commercial names, by the same or different companies. The comparability exercise and subsequent approval of 49/55 (89%) biosimilars were based on one or more pivotal phase III trials testing their clinical efficacy. In all, biosimilars were approved on the basis of 55 trials, mostly phase III (42/55, 76%) assessing clinical efficacy; these were mainly equivalence trials (31/55, 56%). The pivotal phase III trials assessed surrogate measures of clinical effect, and 71% reported immunogenicity data. CONCLUSION:Analysis of the approval of biosimilars in Europe depicts a complex and heterogeneous scenario. The requirement for showing similarity in terms of clinical efficacy and safety provides a robust demonstration of comparable clinical outcomes but lays a burden on biosimilar manufacturers and may delay the introduction of the drugs. The development, licensing, and monitoring of biosimilars would benefit from new strategies to accelerate access to these drugs while reducing uncertainties about their use in practice.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Allocati E,Bertele' V,Gerardi C,Garattini S,Banzi Rdoi
10.1007/s00228-019-02805-ysubject
Has Abstractpub_date
2020-04-01 00:00:00pages
557-566issue
4eissn
0031-6970issn
1432-1041pii
10.1007/s00228-019-02805-yjournal_volume
76pub_type
杂志文章,评审abstract::The effect of grapefruit juice on the urinary excretion of 7-hydroxycoumarin after oral administration of 10 mg coumarin, as an index of cytochrome P450 dependent coumarin metabolism, has been investigated in an open, randomised cross over study in 13 healthy volunteers (7 female, 6 male). The percentage of 7-hydroxyc...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00199885
更新日期:1994-01-01 00:00:00
abstract::The pharmacodynamic effects of torasemide, a new potent loop diuretic, were compared with those of furosemide in a double blind controlled study in 18 hypertensive patients with oedema of various origins. Given orally for 5 days, torasemide was clinically very effective and well tolerated. On a weight basis, the diure...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00541464
更新日期:1986-01-01 00:00:00
abstract::Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00194948
更新日期:1995-01-01 00:00:00
abstract:OBJECTIVE:The efficacy of beta-adrenergic blocking agents and acetylsalicylic acid in the secondary prevention of myocardial infarction has been well recognized since the beginning of the 1980s. In a previous paper, however, we reported a lower than expected use of these drugs during the period 1982 1988. In 1989 the r...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050446
更新日期:1998-05-01 00:00:00
abstract::Twenty patients (5 females, 15 males) with severe heart failure (NYHA IV), due to coronary artery disease in 14, and congestive cardiomyopathy in 6, received an intravenous bolus of the calcium blocker nisoldipine 0.2 mg followed by a continuous infusion of 0.2 micrograms.kg-1.min-1. Haemodynamic measurements were per...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00314795
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:The existence of a sex-by-formulation interaction in bioequivalence studies implies that the bioequivalence results (i.e., the test/reference ratio of the pharmacokinetic parameters) obtained in one sex are not similar to those obtained in the other sex. Therefore, results obtained in studies including only mal...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-019-02632-1
更新日期:2019-06-01 00:00:00
abstract::The role of acetylator phenotype in determining the response to hydralazine when it was added to diuretic and beta-blocker at doses not exceeding 200 mg daily was examined in 57 hypertensive patients. 81% of rapid acetylators needed 200 mg hydralazine daily compared to 38% of slow acetylators (p less than 0.01). Despi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00546706
更新日期:1984-01-01 00:00:00
abstract::A four-period, two-panel, single-rising-dose study (0.1-100 mg) was conducted in healthy males to investigate the pharmacodynamics, tolerability and pharmacokinetics of MK-0434, a steroid 5 alpha-reductase inhibitor. MK-0434 was associated with a significant reduction in dihydrotestosterone, which was maximal at 24 h ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00199874
更新日期:1994-01-01 00:00:00
abstract::The number of marketed non-steroidal anti-inflammatory agents varies widely from one European country to another, partly as a consequence of differing regulatory policies. During a four-year period, nine of 18 applications to market such drugs in the Netherlands failed; the remaining nine compounds were all licenced; ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558371
更新日期:1981-01-01 00:00:00
abstract::In this study we have investigated the effect of co-dergocrine, a selective DA2-agonist, on plasma aldosterone concentrations (PAC) in twelve patients with essential hypertension both in basal conditions and during sodium depletion. Sodium depletion resulted in an increase of PAC from 38 (13) pg/ml to 297 (21) pg/ml. ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00558273
更新日期:1988-01-01 00:00:00
abstract::In 12 patients undergoing coloscopy, 0.5 mg digoxin in aqueous alcoholic solution was injected into the transverse colon. The late maximum of the blood level curve at about 2 hours after the administration suggested delayed absorption of the glycoside. However, the 24 hour urinary excretion of 17 +/- 3.4% in 8 patient...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00614003
更新日期:1975-12-19 00:00:00
abstract:PURPOSE:Sitagliptin, a dipeptidyl peptidase (DPP)-IV inhibitor approved for the treatment of type 2 diabetes, is reported to be more efficacious in Indian patients than non-Indian patient population. The objective of the study was to evaluate pharmacokinetic and pharmacodynamic (PK/PD) parameters of single-dose sitagli...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-018-2433-5
更新日期:2018-05-01 00:00:00
abstract:INTRODUCTION:Regulation EU 536/2014 EU introduces a separation between two parts (technical-scientific aspects and locally relevant ethical aspects) in the assessment of applications for approval of trials and provides for each 'Member State concerned' to arrive at 'one single decision' regarding the application for au...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-016-2009-1
更新日期:2016-04-01 00:00:00
abstract:OBJECTIVE/METHODS:The metabolism of chloramphenicol succinate (CAPS) by human bone marrow was studied in vitro using 75 marrow samples. Whole marrow samples were incubated with CAPS with or without reduced nicotinamide adenine dinucleotide phosphate for 1, 2 and 3 h at 37 degrees C. Ficoll-paque-separated marrow mononu...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280000143
更新日期:2000-08-01 00:00:00
abstract:PURPOSE:As an inhibitor of HMG-CoA reductase that catalyses the first step of cholesterol synthesis, pitavastatin undergoes little hepatic metabolism; however, it is a substrate of uptake and efflux transporters. Since pitavastatin is potentially co-administered with agents that affect transporter activities, the pharm...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-013-1554-0
更新日期:2013-11-01 00:00:00
abstract::The gastric inhibitory effects of CM57755, a new histamine H2 receptor antagonist, have been compared in ten healthy male volunteers with the actions of an equal dose of cimetidine and with placebo. The inhibitory effect of CM57755 was virtually identical with, and not significantly different from the effects of cimet...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00614192
更新日期:1986-01-01 00:00:00
abstract::The pharmacokinetics of ethanol in plasma and whole blood have been investigated and the results used to estimate the volume of total body water (TBW) by means of the dilution principle. Fifteen men (mean age 62 y) were given 0.6 g ethanol/kg body weight as an intravenous infusion over 1 h. The peak concentration of e...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00280133
更新日期:1992-01-01 00:00:00
abstract:OBJECTIVE:We recently reported a highly stereoselective increase in plasma concentrations of (S)-atenolol during exercise which is most likely due to a release of the drug from adrenergic cells. The objective of the present study was to investigate the influence of physical exercise on plasma concentrations of the (R)-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050119
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) is a delayed infrequent potentially life-threatening idiosyncratic drug reaction. Aromatic anticonvulsants and allopurinol are the most frequent causative agents. However, various reports of antibiotic-induced DRESS are available. In this...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-020-03005-9
更新日期:2020-10-06 00:00:00
abstract::The pharmacokinetics of oral L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was studied in 7 normal subjects and 7 patients with familial amyloid polyneuropathy. Each person swallowed a single 300 mg dose in the fasting state, and L-threo-DOPS in plasma and urine was determined by high performance liquid chromatogra...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00605999
更新日期:1982-01-01 00:00:00
abstract::We have evaluated the pharmacokinetics of high doses of clonidine, as used in the prophylactic treatment of alcohol withdrawal syndrome, in 11 alcohol-dependent patients undergoing surgery for oesophagogastrectomy. Clonidine was given in a bolus of 150 micrograms followed by a continuous infusion. After a mean period ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315500
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:There are concerns regarding appropriate use of antibiotics in dentistry practice. Data on dental antibiotic prescribing patterns by dentists is relatively limited. This nationwide study aimed to examine dentists' antibiotic prescriptions in a diagnosis-based manner in Turkey. METHODS:This retrospective study ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-017-2258-7
更新日期:2017-08-01 00:00:00
abstract::Propranolol (P) and all of its major known metabolites were found in maternal plasma, cord plasma and neonatal plasma in 10 women at term, irrespective of the P doses administered and the time elapsed (up to 15 h) between administration of the last P dose and delivery. The ratios of cord plasma to simultaneous materna...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00607078
更新日期:1983-01-01 00:00:00
abstract:PURPOSE:In this review, we focus on the clinical and radiological aspects related to the biological therapy of ankylosing spondylitis (AS), axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). METHODS:A review was carried out in the main medical databases to evaluate the available literature. RESULTS:Even if ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-014-1706-x
更新日期:2014-09-01 00:00:00
abstract:AIMS:The goal of this study was to analyze persistence and the treatment-free interval in patients being prescribed biological drugs in rheumatology practices in Germany. METHODS:Patients who received a first prescription of biological drugs between 2008 and 2016 in 21 rheumatologists in Germany were included in this ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-019-02627-y
更新日期:2019-05-01 00:00:00
abstract::The effect of indenolol on heart rate and blood pressure at rest and after submaximal workload has been studied in 19 patients with established essential hypertension. A stepwise increase from moderate to submaximal exercise was chosen to mimic challenges normally occurring in daily life. After 4 weeks of once a day i...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00544058
更新日期:1985-01-01 00:00:00
abstract::The most convenient route of drug administration is peroral. To reach their target, drug molecules must be absorbed from the gastrointestinal tract and enter the systemic circulation in sufficient quantities. For this reason, understanding and anticipating the mechanisms and factors affecting gastrointestinal absorpti...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s002280100369
更新日期:2001-11-01 00:00:00
abstract:OBJECTIVE:To assess the effect of an intervention on general practitioners' (GPs) knowledge about the diagnosis and treatment of asthma, including the prescribing of anti-asthmatic drugs, and asthmatic patients' knowledge about their disease. METHODS:The study took place in the south-west region of Stockholm County. I...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050361
更新日期:1997-01-01 00:00:00
abstract::The possible interaction between cetirizine 2 HCl and alcohol was studied in a double-blind, cross-over trial in 36 healthy volunteers. The performance of each volunteer was tested with a battery of five objective psychometric tests, and their subjective feelings were evaluated by visual analogue scales, and by extens...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00615227
更新日期:1988-01-01 00:00:00
abstract:OBJECTIVE:UDP-glucuronosyltransferases (UGTs) UGT1A9 and UGT2B7 are involved in the metabolism of antimalarial dihydroartemisinin and antiretroviral zidovudine. Our aim was to analyze the prevalence of UGT1A9 (chromosome 2) and UGT2B7 (chromosome 4) nonsynonymous single nucleotide polymorphisms (SNPs) in West African (...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-006-0206-z
更新日期:2007-01-01 00:00:00