Towards precision medicine
Yann Joly, Bartha Maria Knoppers in Routledge Handbook of Medical Law and Ethics, 2014
Orphan drug designation is typically given to products intended to be the first treatment for a rare and/or serious disease. It is estimated that there are between 4,000 and 5,000 rare diseases worldwide for which no treatment is currently available (Sharma et al. 2010). In the Orphan Drug Act of 1983, the US defines an orphan disease as one affecting less than 200,000 people (approximately 0.06 per cent of the American population). The EU defines a rare disease as affecting 5 per 10,000 citizens (0.05 per cent), while Japan’s definition of rarity involves fewer than 50,000 patients (approximately 0.03 per cent) (Regulation (EC) No. 141/2000; Japan Pharmaceutical Manufacturers Association (JPMA) 2013). Other conditions also affect the granting of orphan drug status. In the EU, a drug must provide diagnosis, prevention or treatment of life-threatening, seriously debilitating, or serious and chronic conditions such that without incentive-driven policies, the drug would be unlikely to generate sufficient returns to justify the necessary investment and there would be no satisfactory medication for the condition. In Japan, the drug must either treat a disease condition for which there are no other treatments available or be clinically superior to a previously accepted drug (EMA 2011; Sharma et al. 2010; JPMA 2013).
Bayesian Frameworks for Rare Disease Clinical Development Programs
Emmanuel Lesaffre, Gianluca Baio, Bruno Boulanger in Bayesian Methods in Pharmaceutical Research, 2020
These definitions arise from regional legislative acts. The earliest such regulation was established in United States, the 1983 Orphan Drug Act. The orphan drugs referred to in the act are for rare diseases or conditions, including biological products and antibiotics “orphaned” (abandoned) by drug companies due to their low sales potential, an obvious consequence of disease rarity. Following the establishment of this groundbreaking legislation, rare diseases are now often called “orphan diseases,” and orphan drugs are inclusive of biologic products (though not medical devices). More than a decade later, the second major related legislative action was the 1999 Orphan Regulation adopted by the European Parliament. Both regulations include monetary incentives, marketing exclusivities, and clinical research assistance for rare disease medicinal product development. Other than drug product development, there are other regulations or government entities (e.g. the US Rare Diseases Act in 1992 and the Spanish Rare Diseases Research Institute) that aid patient support groups and fund research projects in rare diseases. Several papers, including Gupta (2012) and Gammie et al. (2015), synthesize details and comparisons across different legislations across nations. In fact, most developed countries and regions now have well-established rare disease or orphan product programs. The US remains one of the leaders and a key player in orphan product development and rare disease research.
Impact of Evolving Regulatory Pathways on Statistical Considerations in Oncology Clinical Trials
Satrajit Roychoudhury, Soumi Lahiri in Statistical Approaches in Oncology Clinical Development, 2018
During different stages of the drug development, the manufacturing company or the sponsor of the drug product can apply for orphan drug, fast track, and breakthrough designations. The orphan drug designation is given to products that are being developed for use in orphan diseases with a disease prevalence of less than 200,000 patients per year in the United States. This designation provides an extended market exclusivity and waiver of the application review fee. A fast track designation is based on observed preclinical activity and allows for rolling submission of different sections of the marketing application. The breakthrough designation [1] (Food and Drug Safety Innovation Act 2012) allows FDA to expedite and assist drug manufacturers in the development and review of new drugs with preliminary clinical evidence that suggests that the drug may offer substantial improvement over available therapies for patients with serious or life-threatening diseases [2] (FDA guidance 2014).
Orphan medicinal products’ access to the Bulgarian pharmaceutical market – challenges and obstacles
Published in Expert Opinion on Orphan Drugs, 2018
Maria Kamusheva, Konstantin Tachkov, Guenka Petrova, Alexandra Savova, Manoela Manova
Drummond highlights the challenges in the evaluation of the cost-effectiveness for orphan medicines and recommends the development of appropriate funding mechanisms. Drummond stresses the necessity of assessing the social benefit of health technology, not just the value of the incremental ratio. The social benefit and ethical considerations for most of the orphan medicines are leading criteria in the process of their assessment [1]. The application of multi-criteria decision analysis [28] to define the added value of orphan drugs could ensure better evaluation of these drugs especially in the Central and Eastern European countries so that they could overcome the greater financial burden of these drugs [29–32]. Despite the lack of specific higher threshold, specific indications and evaluated parameters for orphan drugs are included in the HTA guideline in Bulgaria: moral and ethical considerations should be taken into account and the recommendation for inclusion could be positive despite the high costs and no proven cost-effectiveness of an orphan medicine [10]. This could be explained by the fact that many of the conditions are chronic, inherited, and require therapy for life. It is expected that orphan drugs will improve the patients’ health status or quality of life.
Cost-effectiveness of defibrotide for treatment of severe veno-occlusive disease: it is time for evidence based economic evaluations
Published in Journal of Medical Economics, 2021
Alois Gratwohl
Approval of Defibrotide by EMA and FDA was facilitated by its orphan drug status. “Orphan drug status” was introduced 30 years ago as an incentive for the pharmaceutical industry to develop novel drugs for rare diseases. The initiative was clearly successful; a multitude of novel drugs has been registered worldwide since. This success is accompanied by a downside. Costs for orphan drugs might bring a solidarity-based health care system to its limits. Prizing of orphan drugs is not based on the costs for research, development and production. It rather follows a sum, representing the willingness in a respective country to pay for the years of life saved. This problem is not restricted to Defibrotide. The concept has become generally accepted, but is now of concern worldwide and intensively discussed: what is a reasonable price for an orphan drug? [13–15]. These arguments are valid on the assumption that the drug will help the patient to gain years of life.
The potential and benefits of repurposing existing drugs to treat rare muscular dystrophies
Published in Expert Opinion on Orphan Drugs, 2018
Hesham M. Ismail, Olivier M. Dorchies, Leonardo Scapozza
A tool that can help in shortening cost and time in developing therapies for rare diseases is the orphan drug designation (ODD). In 1983, the Orphan Drug Act law was passed in the United States for structuring the framework of incentives provided for the engagement in developing therapies for diseases that have been largely overlooked. The FDA, through its Office of Orphan Products Development, is responsible for evaluating the scientific and clinical projects aiming to identify and investigate products for rare diseases. Orphan status is given to drugs or biologics intended for safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the United States, or that affect more than 200,000 persons but are not expected to recover the costs of developing of a drug (for a detailed description refer to the FDA website). As a result of the implementation of this program and the encouragement given, the development of more than 600 drugs and biological products for rare diseases were enabled since 1983.
Related Knowledge Centers
- Cancer Treatment
- Pharmacodynamics
- Pharmacokinetics
- Medication
- Rare Disease
- Medical Research
- Profit Motive
- Biopharmaceutical
- Orphan Drug Act of 1983
- Dosing