Orphan medicinal products in Europe and United States to cover needs of patients with rare diseases: an increased common effort is to be foreseen.

BACKGROUND: In the European Union (EU) and United States (US), specific regulations have been released to provide incentives to develop and sell orphan medicinal products. We analysed the status of orphan drugs designated that not yet received a marketing authorisation or already marketed for patients affected by rare diseases in the EU and US up to December 2015. For each drug, the following data were extracted: designation date, active substance(s), orphan condition and indication, trade name, approved therapeutic indication, approved ages, genetic nature of disease and if affects children. RESULTS: In the EU, 1264 Orphan Drug Designations have been granted and 133 medicinal products were approved covering a total of 179 indications and 122 rare conditions. Among these, 79 were approved under Regulation (EC)141/2000 (65 still listed in the Orphan Medicinal Products Register and 14 lost the orphan designation but still authorised) and 23 were approved centrally by the European Agency before the Orphan Regulation entered into force. On the other hand, in the US 3082 designations and 415 orphan products, covering a total of 521 indications and 300 rare conditions, were granted. As a result, the mean of designations per year is 79 in the EU and 93.4 in the US, while the mean of approved indications per year is 8.5 in the EU and 15.8 in the US. No orphan product is marketed in the EU for bone and connective tissue, ophthalmic, poisoning/overdose, renal, urinary and reproductive rare diseases. Among the marketed medicinal products, only 46.6% in the EU and 35.2% in the US are approved for children. If all the existing market approvals were merged, 362 additional therapeutic indications in the EU and 72 in the US would be covered. CONCLUSIONS: Our data show that notwithstanding the incentives issued, the number of medicines for rare diseases is still limited, and this is more evident in certain therapeutic areas. However, by merging all the existing approvals, patients would benefit of substantial advantages in both geographic areas. Efforts and cooperation between EU and US seem the only way to speed up the development and marketing of drugs for rare diseases.

Role of early symptoms in assessment of syncope in elderly people: results from the Italian group for the study of syncope in the elderly.

OBJECTIVES: To assess the ability of specific early symptoms to predict cardiac and noncardiac syncope in elderly people. DESIGN: Multicenter cross-sectional observational study. SETTING: Inpatient geriatric acute care departments and outpatient clinics. PARTICIPANTS: Two hundred forty-two patients with syncope (mean age 79+/-8) consecutively referred for evaluation of transient loss of consciousness to any of six clinical centers participating in the Italian Group for the Study of Syncope in the Elderly (GIS Study). MEASUREMENTS: All patients were assessed according to European Society of Cardiology Syncope guidelines and interviewed about symptoms and signs present before syncope. RESULTS: One hundred seventy-four of 242 patients (75.4%) had noncardiac syncope, and 34 (14.7%) had cardiac syncope; 165 patients (71.1%) related symptoms before the loss of consciousness. When elderly patients with syncope were stratified for the presence and absence of symptoms, noncardiac syncope showed the highest prevalence of symptoms (75.3%, P<.01). Awareness of being about to faint, sweating, blurred vision, and nausea are more prevalent in noncardiac syncope. Dyspnea is more prevalent in cardiac syncope. All symptoms except awareness of being about to faint and weakness had good specificity, but sensitivity was low for all symptoms considered. Multivariate regression analysis adjusted for sex and age indicated that nausea (relative risk (RR)=3.7, 95% confidence interval (CI)=1.26-11.2), blurred vision (RR=3.5, 95% CI=1.34-9.59), and sweating (RR=2.8, 95% CI=.21-6.89) were predictive of noncardiac syncope. Dyspnea (RR=5.5, 95% CI=1.0-30.2) was the only symptom predictive of cardiac syncope. CONCLUSION: The data show that symptoms such as nausea, blurred vision, and sweating are predictive of noncardiac syncope, whereas only dyspnea is predictive of cardiac syncope in elderly people.