Predictors of orphan drug approval in the European Union

Objective: To encourage the development of drugs for rare diseases, orphan drug legislation has been introduced in the USA (1983) and in the EU (2000). Recent literature discusses factors that may influence the development of new orphan medicinal products in the EU. This study aims to identify predictors for successful marketing authorisation of potential orphan drugs in the EU. Methods: A comparison between randomly selected authorised and a matched sample of not-yet-authorised orphan drug designations has been performed. Determinants in the study included characteristics of the indication, of the product and of the sponsor. Data were collected from the public domain only. Results: Orphan drug approval was strongly associated with previous experience of the sponsor in obtaining approval for another orphan drug (OR=17.3, 95% CI=5.6-53.1). Furthermore, existing synthetic entities compared to biotechnology products tended to have a higher likelihood of reaching approval status (OR=3.9, 95% CI=0.9-16.6). Conclusion: This study showed that experience of a company in developing orphan drugs is an important predictor for subsequent authorisation of other orphan drugs. The same applies for existing (synthetic) molecules, for which much knowledge is available. Further research should be directed towards studying the quality of the clinical development program of those designated orphan medicinal products not reaching approval status

Reflections on the Future of Pharmaceutical Public-Private Partnerships : From Input to Impact

Public Private Partnerships (PPPs) are multiple stakeholder partnerships designed to improve research efficacy. We focus on PPPs in the biomedical/pharmaceutical field, which emerged as a logical result of the open innovation model. Originally, a typical PPP was based on an academic and an industrial pillar, with governmental or other third party funding as an incentive. Over time, other players joined in, often health foundations, patient organizations, and regulatory scientists. This review discusses reasons for initiating a PPP, focusing on precompetitive research. It looks at typical expectations and challenges when starting such an endeavor, the characteristics of PPPs, and approaches to assessing the success of the concept. Finally, four case studies are presented, of PPPs differing in size, geographical spread, and research focus

Veiligheidswaarschuwingen voor weesgeneesmiddelen in de Europese Unie en de Verenigde Staten

Objective: To determine the frequency and nature of safety-related regulatory actions for orphan drugs in the United States and the European Union. Orphan drugs are often intended for serious or chronically debilitating diseases. None of the studies that have been conducted on safety-related regulatory actions for drugs focused on orphan drugs. Design: Cohort study. Methods: Orphan drugs approved in the United States and/or the European Union between January 2000 and December 2007 were identified (75 US, 44 EU, of which 24 in both regions). Nature, frequency and timing of safety-related regulatory actions were determined for each orphan drug, defined as safety withdrawals, black box warnings, and written communications to healthcare professionals issued by the FDA or the EMA between January 2000 and June 2008. Results: Of the 95 identified orphan drugs 10 (11%) received at least one safety-related regulatory action. No safety withdrawals, 4 black box warnings and 12 written orphan drugs were identified. Probability of a first safety-related regulatory action for orphan drugs was 20% after 8 years of follow-up. Orphan drugs approved by accelerated approval [relative risk (RR) 3.3; 95% CI 1.1 to 10.4), oncologic products (RR 7.8; 95% CI 1.0-63.8) and products for gastrointestinal and metabolism indications (RR 10.4; 95% CI 1.3-87.3) may have a higher risk for a safety-related regulatory action. Conclusion: The probability of a first safety-related regulatory action of an orphan drug was slightly lower than reported for biologicals and new molecular entities. However, detection of safety issues may be complicated by the limited experience with orphan drugs in practical use. Copyright Adis Data Information 2010. All rights reserved

Veiligheidswaarschuwingen voor weesgeneesmiddelen in de Europese Unie en de Verenigde Staten

Objective: To determine the frequency and nature of safety-related regulatory actions for orphan drugs in the United States and the European Union. Orphan drugs are often intended for serious or chronically debilitating diseases. None of the studies that have been conducted on safety-related regulatory actions for drugs focused on orphan drugs. Design: Cohort study. Methods: Orphan drugs approved in the United States and/or the European Union between January 2000 and December 2007 were identified (75 US, 44 EU, of which 24 in both regions). Nature, frequency and timing of safety-related regulatory actions were determined for each orphan drug, defined as safety withdrawals, black box warnings, and written communications to healthcare professionals issued by the FDA or the EMA between January 2000 and June 2008. Results: Of the 95 identified orphan drugs 10 (11%) received at least one safety-related regulatory action. No safety withdrawals, 4 black box warnings and 12 written orphan drugs were identified. Probability of a first safety-related regulatory action for orphan drugs was 20% after 8 years of follow-up. Orphan drugs approved by accelerated approval [relative risk (RR) 3.3; 95% CI 1.1 to 10.4), oncologic products (RR 7.8; 95% CI 1.0-63.8) and products for gastrointestinal and metabolism indications (RR 10.4; 95% CI 1.3-87.3) may have a higher risk for a safety-related regulatory action. Conclusion: The probability of a first safety-related regulatory action of an orphan drug was slightly lower than reported for biologicals and new molecular entities. However, detection of safety issues may be complicated by the limited experience with orphan drugs in practical use. Copyright Adis Data Information 2010. All rights reserved

5′-Amino Acid Esters of Antiviral Nucleosides, Acyclovir, and AZT Are Absorbed by the Intestinal PEPT1 Peptide Transporter

Purpose . General use of nucleoside analogues in the treatment of viral infections and cancer is often limited by poor oral absorption. Valacyclovir, a water soluble amino acid ester prodrug of acyclovir has been reported to increase the oral bioavailability of acyclovir but its absorption mechanism is unknown. This study characterized the intestinal absorption mechanism of 5′-amino acid ester prodrugs of the antiviral drugs and examined the potential of amino acid esters as an effective strategy for improving oral drug absorption.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41466/1/11095_2004_Article_303953.pd