Orphan drugs development

Haffher, M. (1998). Orphan drug development—International program and study design issues. Drug Information J. 32 93-99. 

In order to encourage pharmaceutical companies to invest in orphan drug development, legislation provides for a number of incentives. These include application fee waiver (the extent of reduction varies with the region of the world, and in the European Union it is 50% for all fees since 2002), market exclusivity and protocol assistance. In the European Union, there is 100% reduction in the fee applicable to the provision of any scientific advice. The fund made available by the Community for fee exemptions for orphan medicinal products amounts to= 3 700000 in 2005. 

Brief History of the Office of Orphan Drug Development, www.fda.gov/ orphan/History.htm, accessed 15 June 2006. 

This FDA Orphan-Drug Review checklist has been designed in consultation with FDA reviewers, industry consultants, and regulatory professionals to serve as a summary tool indicating the evaluative criteria used by the Office of Orphan-Drug Development to critique and assess applications received. It can be used internally as a part of the Quality Assurance process, as a guideline for regulatory development of an application, and/or as a self-assessment tool to predict likely FDA response to an application. 

Food and Drug Administration assistance to orphan drug developers in protocol design for new drug approval (NDA) or product license approval (PLA) applications 28... 

Spitz, Diamines and Higher Amines, Aliphatic in Kirk-Othmer Encyclopedia of Chemical Technology vol. 7 (Wiley-Interscience, New York. 3rd ed., 1979) pp 580-602. Orphan drug developed by Merck. Review. J. M. Walshe, Orphan Drugs, F. E. Karch, Ed. (Marcel Dekker, New York, 1982) Pp 57-71-... 

There are eight principal stakeholders in orphan drug development. Note that many can be either public or private institutions, as well as either individuals or larger groups. These stakeholders often have different motives. 

Orphan drug development may not be required if the drug is already marketed for a more... 

Pastores GM, Gupta P (2013) Orphan drug development. Pediatr Endocrinol Rev ll(Suppl l) 64-67... 

The Orphan Drug Act of 1983 was passed to encourage die development and marketing of products used to treat rare diseases. The act defines a rare disease as a condition affecting fewer than 200,000 individuals in die United States. The National Organization of Rare Disorders reports that there are more tiian 6000 rare disorders that affect approximately 25 million individuals. Examples of rare disorders include Tourette s syndrome, ovarian cancer, acquired immunodeficiency syndrome (AIDS), Huntington s disease, and certain forms of leukemia... 

Pharmaceutical innovation has made a decisive contribution to the reduction of mortality and the improvement of quality of life. The role of patents in providing incentives for innovation has been crucial. Yet at the same time there are limitations that need to be overcome in the future. Here we will mention just two examples orphan drugs and parallel imports. Patents do not offer incentives to develop drugs for low-prevalence diseases, known as orphan drugs. Governments are sometimes faced with the option of public production, as the private sector does not invest in them. Yet these would be precisely the cases in which experiments would be conducted with new models for promoting innovation, as discussed in this chapter. 

Currently, there are a number of systemic and intestine-selective MTP inhibitors, including lomitapide (23, BMS-201038, AEGR-733), implitapide (24), JTT-130, SLx-4090, and R-256918 (latter three structures not disclosed) believed to be in active development [60]. In a meta-analysis of three Phase II clinical trials, lomitapide as monotherapy or in combination with ezetimibe, atorvastatin, or fenofibrate significantly reduced LDL cholesterol (up to 35% as monotherapy and 66% in combination with atorvastatin) and was well tolerated with less than 2% discontinuation due to abnormal liver function [61]. Lomitapide has also been granted orphan drug status for the treatment of homozygous familial hypercholesterolemia [59]. Results of a Phase II study of JTT-130 for type 2 diabetes are expected in August 2010 [59,60]. 

The development of drugs for these diseases, intended for a limited number of patients, often requires considerable research, and is consequently costly. A particular approach of ethical, political and economical problems relevant for development and disposal of orphan drugs is also required. 

Periodically Congress has permitted the use of tax credits as a direct reduction from income taxes. Examples are tax credits for installing energy conservation devices, use of alcohol fuels and electric vehicles, development of orphan drugs, creation of low-income housing, and some research expenditures. Tax credits have been used historically to stimulate capital investment in the United States. Such deductions are more valuable than depreciation because they represent direct deductions from the tax bill after taxes are computed on income. 

Passage of the first Orphan Drug Amendment to encourage development of drugs for small markets. 

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