Article

Drug development for orphan diseases in the context of personalized medicine

Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Mich. 48109-0534, USA.
Translational research : the journal of laboratory and clinical medicine 12/2009; 154(6):314-22. DOI: 10.1016/j.trsl.2009.03.008
Source: PubMed

ABSTRACT

Orphan diseases are diseases that are found in less than 200,000 patients in the United States, which is the cutoff point for the number of patients for a drug to be profitable. Because many thousands of orphan diseases exist in the aggregate (about 20 to 30 million Americans have orphan diseases), these patients are disenfranchised from drug development by the pharmaceutical industry. Orphan drugs are a large part of personalized medicine. The orphan diseases are often so rare that a physician may observe only 1 case a year or less. So proper treatment is a personalized encounter between doctor and patient. Academic physician-scientists have tried to fill this therapy vacuum by working on developing orphan drugs. But many disincentives are involved, which include career disincentives, lack of funding, and the multiple areas of expertise that are required. Positive developments include formation of the National Organization for Rare Diseases, the Orphan Drug Act, the development of a grant program to fund orphan drug development, the formation of the National Institutes of Health Office of Rare Diseases, and the passage of orphan drug legislation by other countries. Progress has increased, but the 300 orphan drugs and devices approved in the last 25 years are still only a drop in the bucket compared with the many thousands of orphan diseases. I believe we must do better. I present my own 2 examples of the positive and the negative aspects of orphan drug development, and I end this article by giving recommendations on how we might succeed both in developing more orphan drugs and in rescuing the pharmaceutical industry from its impending economic collapse.

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    • "Some estimates suggest this category includes over 7000 rare diseases affecting 25–30 million people.56, 57 Even though over 300 orphan drugs have been approved since the passage of the Orphan Drugs Act in 1983, there is still a long way to go until most rare diseases have a treatment.56,57 The recent publicity around the ULTRA act and TREAT act legislation suggests there is considerable interest to promote more research into rare diseases and translational research58,59 and that this may lead to commercial opportunities. "
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    ABSTRACT: The Open Drug Discovery Teams (ODDT) project provides a mobile app primarily intended as a research topic aggregator of predominantly open science data collected from various sources on the internet. It exists to facilitate interdisciplinary teamwork and to relieve the user from data overload, delivering access to information that is highly relevant and focused on their topic areas of interest. Research topics include areas of chemistry and adjacent molecule-oriented biomedical sciences, with an emphasis on those which are most amenable to open research at present. These include rare and neglected diseases, and precompetitive and public-good initiatives such as green chemistry. The ODDT project uses a free mobile app as user entry point. The app has a magazine-like interface, and server-side infrastructure for hosting chemistry-related data as well as value added services. The project is open to participation from anyone and provides the ability for users to make annotations and assertions, thereby contributing to the collective value of the data to the engaged community. Much of the content is derived from public sources, but the platform is also amenable to commercial data input. The technology could also be readily used in-house by organizations as a research aggregator that could integrate internal and external science and discussion. The infrastructure for the app is currently based upon the Twitter API as a useful proof of concept for a real time source of publicly generated content. This could be extended further by accessing other APIs providing news and data feeds of relevance to a particular area of interest. As the project evolves, social networking features will be developed for organizing participants into teams, with various forms of communication and content management possible.
    Full-text · Article · Aug 2012
    • "Positive developments include formation of the National Organization for Rare Diseases, the Orphan Drug Act, the development of a grant program to fund orphan drug development, the formation of the National Institutes of Health Office of Rare Diseases, and the passage of orphan drug legislation by other countries. Progress has increased, but the 300 orphan drugs and devices approved in the last 25 years are still only a drop in the bucket compared with the many thousands of orphan diseases.[1] "
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    ABSTRACT: The growth of pharma industries has slowed in recent years because of various reasons such as patent expiries, generic competition, drying pipelines, and increasingly stringent regulatory guidelines. Many blockbuster drugs will loose their exclusivity in next 5 years. Therefore, the current economic situation plus the huge generic competition shifted the focus of pharmaceutical companies from the essential medicines to the new business model - niche busters, also called orphan drugs. Orphan drugs may help pharma companies to reduce the impact of revenue loss caused by patent expiries of blockbuster drugs. The new business model of orphan drugs could offer an integrated healthcare solution that enables pharma companies to develop newer areas of therapeutics, diagnosis, treatment, monitoring, and patient support. Incentives for drug development provided by governments, as well as support from the FDA and EU Commission in special protocols, are a further boost for the companies developing orphan drugs. Although there may still be challenges ahead for the pharmaceutical industry, orphan drugs seem to offer the key to recovery and stability within the market. In our study, we have compared the policies and orphan drug incentives worldwide alongwith the challenges faced by the pharmaceutical companies. Recent developments are seen in orphan drug approval, the various drugs in orphan drug pipeline, and the future prospectives for orphan drugs and diseases.
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    ABSTRACT: MEDICATION SAFETY Overlooked Renal Dosage Adjustments A retrospective analysis of 647 patients at hospital discharge com-pared required renal dosage adjust-ments to dosage actually prescribed. This study was conducted at VieCuri Medical Centre in Venlo, Netherlands. Patient demographics and renal function data were col-lected, and dosage adjustment needs were assessed via the pharmacy-supported discharge counseling ser-vice. The incidence of inappropriate dosing based on renal function was measured at hospital discharge. Thirty-seven percent of patients evaluated during the study period (237/647) had a creatinine clear-ance less than 51 mL/min/1.73 m 2 ; dosage adjustment was warranted in 23.9% (411/1,718) of prescrip-tions. When dosage adjustment should have been performed, more than 40% of prescriptions (169/411; 41.1%) were inappropri-ate for renal function (9.8% of pre-scriptions overall; 169/1,718). Fur-thermore, 60.4% (102/169) of inappropriate prescriptions pos-sessed the potential for moderate or severe clinical consequences, as evaluated by a panel of two clinical pharmacologists and one nephrolo-gist. Study authors also noted a lack of standardized dosing guidelines for agents requiring renal dosage adjustment. The authors also sug-gested that augmenting medication systems by adding dynamic renal dosing alerts would improve moni-toring. Summary: A comparison of suggested renal dosing and actual dosing at hospital discharge revealed that appropriate prescribing may be overlooked. van Dijk EA, Drabbe NRG, Kruijtbosch M, De Smet PAGM. Drug dosage adjust-ments according to renal function at hos-pital discharge. Ann Pharmacother. 2006;40:1254-1260.
    Preview · Article · Dec 1122 · Hospital pharmacy
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