Background Concerns remain about the safety of adding long-acting β2-agonists to inhaled glucocorticoids for the treatment of asthma. In a postmarketing safety study mandated by the Food and Drug Administration, we evaluated whether the addition of formoterol to budesonide maintenance therapy increased the risk of serious asthma-related events in patients with asthma. Methods In this multicenter, double-blind, 26-week study, we randomly assigned patients, 12 years of age or older, who had persistent asthma, were receiving daily asthma medication, and had had one to four asthma exacerbations in the previous year to receive budesonide-formoterol or budesonide alone. Patients with a history of life-threatening asthma were excluded. The primary end point was the first serious asthma-related event (a composite of adjudicated death, intubation, and hospitalization), as assessed in a time-to-event analysis. The noninferiority of budesonide-formoterol to budesonide was defined as an upper limit of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The primary efficacy end point was the first asthma exacerbation, as assessed in a time-to-event analysis. Results A total of 11,693 patients underwent randomization, of whom 5846 were assigned to receive budesonide-formoterol and 5847 to receive budesonide. A serious asthma-related event occurred in 43 patients who were receiving budesonide-formoterol and in 40 patients who were receiving budesonide (hazard ratio, 1.07; 95% confidence interval [CI], 0.70 to 1.65]); budesonide-formoterol was shown to be noninferior to budesonide alone. There were two asthma-related deaths, both in the budesonide-formoterol group; one of these patients had undergone an asthma-related intubation. The risk of an asthma exacerbation was 16.5% lower with budesonide-formoterol than with budesonide (hazard ratio, 0.84; 95% CI, 0.74 to 0.94; P=0.002). Conclusions Among adolescents and adults with predominantly moderate-to-severe asthma, treatment with budesonide-formoterol was associated with a lower risk of asthma exacerbations than budesonide and a similar risk of serious asthma-related events. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01444430 .).
In many European countries, medicines promotion is governed by voluntary codes of practice administered by the pharmaceutical industry under its own system of self-regulation. Involvement of industry organizations in policing promotion has been proposed to deter illicit conduct, but few detailed studies on self-regulation have been carried out to date. The objective of this study was to examine the evidence for promotion and self-regulation in the UK and Sweden, two countries frequently cited as examples of effective self-regulation.
Maintaining research and development (R&D) productivity at a sustainable level is one of the main challenges currently facing the pharmaceutical industry. In this article, we discuss the results of a comprehensive longitudinal review of AstraZeneca’s small-molecule drug projects from 2005 to 2010. The analysis allowed us to establish a framework based on the five most important technical determinants of project success and pipeline quality, which we describe as the five ‘R’s: the right target, the right patient, the right tissue, the right safety and the right commercial potential. A sixth factor - the right culture - is also crucial in encouraging effective decision-making based on these technical determinants. AstraZeneca is currently applying this framework to guide its R&D teams, and although it is too early to demonstrate whether this has improved the company’s R&D productivity, we present our data and analysis here in the hope that it may assist the industry overall in addressing this key challenge.
Interviewed by Ellen Clarke (Commissioning Editor, Future Science Group). Richard Goodfellow is Joint-CEO of Scancell Holdings plc, a public company listed on the London Stock Exchange. He has over 25 years international experience in the pharmaceutical industry, in Big Pharma and with Biotech companies. During his time at Astra, he oversaw the launch of Losec and other key products internationally. Thereafter, he held the post of Director of Licensing and New Business Development at Scotia Pharmaceuticals, where he was involved with the company’s flotation on the London Stock Exchange and successfully negotiated numerous deals. Goodfellow is also a founder of Paradigm Therapeutics, a Cambridge-based functional genomics company and is a former Director of Enact Pharma plc.
The pharmaceutical industry remains under huge pressure to address the high attrition rates in drug development. Attempts to reduce the number of efficacy- and safety-related failures by analysing possible links to the physicochemical properties of small-molecule drug candidates have been inconclusive because of the limited size of data sets from individual companies. Here, we describe the compilation and analysis of combined data on the attrition of drug candidates from AstraZeneca, Eli Lilly and Company, GlaxoSmithKline and Pfizer. The analysis reaffirms that control of physicochemical properties during compound optimization is beneficial in identifying compounds of candidate drug quality and indicates for the first time a link between the physicochemical properties of compounds and clinical failure due to safety issues. The results also suggest that further control of physicochemical properties is unlikely to have a significant effect on attrition rates and that additional work is required to address safety-related failures. Further cross-company collaborations will be crucial to future progress in this area.
Research and development (R&D) collaborations represent one approach chosen by the pharmaceutical industry to tackle current challenges posed by declining internal R&D success rates and fading of the blockbuster model. In recent years, a flexible concept to collaborate in R&D has emerged: virtual pharmaceutical companies (VPCs). These differ from other R&D companies, such as biotech start-ups, collaborating with big pharmaceutical companies, because they solely comprise experienced teams of managers. VPCs have only been described anecdotally in literature. Thus, we present here the characteristics of a VPC and suggest how big pharma can leverage the concept of VPCs by introducing five possible modes of collaboration. We find that one mode, investing, is particularly promising for big pharma.
Medullary thyroid cancer (MTC) represents an aggressive form of thyroid malignancy. Some may occur spontaneously or can be associated with Multiple Endocrine Neoplasia syndromes, or Familial Medullary Thyroid Cancer syndrome. In these patients, the protooncogene RET (rearranged during transfection) is mutated. In patients who have unresectable or metastatic disease, the long term prognosis is poor. New treatments for this disease have focused on the use of targeted agents that inhibit the receptor tyrosine kinase of RET. One of these treatments, Vandetanib (Caprelsa, Astra Zeneca), recently has received approval from the Food and Drug Administration for the treatment of patients with progressive locally advanced and/or metastatic disease. This review highlights the studies that led to the drug’s approval, and discusses on the potential financial costs of treatment and side effects of this therapy. The main clinical studies evaluating Vandetanib for the treatment of other solid tumors will also be reviewed.
Simultaneous determination of rosuvastatin and propranolol in their binary mixture by synchronous spectrofluorimetry
- Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
- Published 7 months ago
Simultaneous determination of rosuvastatin calcium and propranolol hydrochloride using the first derivative synchronous spectrofluorimetry was described. This method involves measuring the synchronous fluorescence of both drugs in ethanol using, ∆ λ = 60 nm then the first derivative was recorded and the peak amplitudes were measured at 350 and 374 nm for rosuvastatin calcium and propranolol hydrochloride, respectively. Under the optimum conditions, the linear ranges of rosuvastatin calcium and propranolol hydrochloride were 0.2-2 μg/mL and 0.1-1 μg/mL, respectively. The method was used for quantitative analysis of the drugs in raw materials and pharmaceutical dosage form. The validity of the proposed method was assessed according to an international conference on harmonization (ICH) guidelines.
Esomeprazole is the S-isomer of omeprazole, used to treat gastro esophageal reflux disease. It is one of the widely manufactured and marketed drugs by many pharmaceutical companies in Bangladesh. The aim of the study is to compare the different physical parameters including hardness, friability, diameter, thickness, disintegration time, dissolution test and assay for quality evaluation and characterization of tablets of five different brands of Bangladeshi pharmaceutical company. The specified compendial method was followed for their evaluation test.
The budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) is an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist fixed-dose combination formulated with innovative co-suspension delivery technology that is in clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, Phase I, single-dose, six-treatment, four-period, crossover study (NCT01980615) examined the pharmacokinetic (PK) and safety profile of three doses of BGF MDI (320/14.4/10 μg [equivalent to budesonide/glycopyrrolate/formoterol fumarate 320/18/9.6 μg], 160/14.4/10 μg and 80/14.4/10 μg), two doses of a budesonide/formoterol fumarate dihydrate fixed-dose combination (BUD/FORM MDI 320/9 μg and 160/9 μg; not using co-suspension delivery technology) and a glycopyrronium/formoterol fumarate dihydrate co-suspension delivery technology MDI (GFF MDI 14.4/10 μg) in healthy volunteers (18-45 years of age). PK parameters included area under the plasma concentration-time curve from 0 to 12 h (AUC0-12), AUC up to the last measurable concentration (AUC0-t), maximum plasma concentration (Cmax) and time to maximum plasma concentration (tmax). Safety was monitored throughout the study. Of 84 subjects randomized, 76 completed the study. BGF MDI 320/14.4/10 μg was bioequivalent to BUD/FORM MDI 320/9 μg for budesonide for Cmax, AUC0-12and AUC0-t(primary objective). Dose proportionality was observed for the budesonide component between BGF MDI 80/14.4/10 μg and BGF MDI 160/14.4/10 μg, and between BGF MDI 160/14.4/10 μg and BGF MDI 320/14.4/10 μg. Systemic exposure to glycopyrronium and formoterol after BGF MDI 320/14.4/10 μg treatment was similar to GFF MDI 14.4/10 μg. The rate of adverse events was 3.7-17.9% across treatments without any serious adverse events. In conclusion, BGF MDI 320/14.4/10 μg had a similar budesonide PK profile to BUD/FORM MDI 320/9 μg. No PK drug-drug interactions were observed when budesonide was added to glycopyrronium and formoterol fumarate dihydrate. These data support the use of budesonide 320 μg and 160 μg in future clinical trials of BGF MDI in COPD.