Masterstudiengang "Drug Regulatory Affairs"


An overview of the incentives in the EU and USA and their draw backs to promote drugs for the treatment of rare diseases ***

Dr. Laurent Schmitt (Abschlußjahr: 2012)

Language: English

Currently, the number of rare diseases is estimated between 5,000 and 7,000 with approximately 250 new diseases being described on an annual basis. The combined number of people suffering from rare diseases in the European Union (EU) and United States (US) is estimated to exceed 55 million. Rare disorders are considered a real health issue.

The Orphan Drug Act has been adopted in the USA in 1983 to promote research and development for drugs treating rare diseases. In 2000, a similar regulation, Regulation (EC) No 141/2000, was adopted in EU.

The designation of "‘orphan drug"’ status is based on two criteria:

  1. Epidemiological criterion: it sets a prevalence threshold to classify the disease as rare. The threshold is « less than 200'000 persons in the US (about 0.75 ‰), less than 5/10'000 in EU (0.5 ‰).
  2. Economic criterion: For a given product, irrespective of disease prevalence, there is no reasonable expectation that R&D and production costs will be fully recovered by sale revenues in the country where orphan status is granted.

Orphan drug designation opens the right to incentives promoting the development before the marketing authorisation (push mechanisms) : they consist of free protocol assistance for clinical trials, fast-track procedures, registration fees exemption, research grants, and additionally in the US, tax credit and grants funding for clinical and nonclinical trials. After the marketing authorisation (pull mechanisms), a market exclusivity applies, to protect the market from any competitor for the rare disease indication: 7 years in USA, 10 years in EU. Moreover, a higher market price than classical drugs is accepted due to the small market size.

Statistical surveys showed clearly that the orphan drug regulations in US and EU successfully encouraged the pharmaceutical industry in developing treatments for rare diseases.
The most represented therapeutic areas for orphan drugs are found in oncology. Through the characterisation of different cancer types, including the precise identification of the mutated genes, it has been possible to define rare cancers based on their prevalence. Some known cytostatic drugs have been developed to address these rare cancers and could receive the orphan drug designation and marketing authorisation. In this context, the same drug could receive multiple ODD. Through this example, one can already envision that the prevalence issue is inevitably growing more complex with the advent of pharmacogenomics and personalized medicine. Combined with high pricing accepted for orphan drugs, this situation captivates a high interest from the pharmaceutical industry. High price of orphan does not appear to be caused by a monopoly induced by the market exclusivity, but is due to lack of interest from competitors due to the small size of the orphan drug market. However, a regulation of excessive profits should be considered, possibly through a shorter marketing exclusivity, to restore the original spirit of the Orphan Drug Act.

Significant improvement in clinical studies have been made. Clinical studies were adapted to the orphan disease equation : how to recruit enough patients to carry out the necessary clinical studies? The use of surrogate endpoints lead to accelerated approvals and lower clinical studies costs.

Diagnostics have been found to be essential in the improvement of the patients conditions. Earlier detection of rare diseases would be improved with better diagnostic tools essentially based on pharmacogenomics, but also with the creation of networks from the OD patients associations, and better trained physicians.

One approach to speed up research at affordable costs consists in finding new uses for existing drugs. It is called drug repositioning/repurposing. It involves High Throughput Screening of known active pharmaceutical ingredients in-vitro, but also in-silico. The FDA created a comprehensive database, the Rare Diseases Repurposing Database by matching the FDA orphan designation database to the FDA drug and biological product approval lists. In fact, a more global database with data from international origines would probably contribute to a higher success in drug repurposing.

Another aspect relates to the pricing and reimbursement procedures. In EU patients do not have the same access to orphan drugs since pricing and reimbursement are handled at a national level. With the increasing personalized medicines, pricing and reimbursement become a bigger issue for health care systems due to the high costs of orphan drugs. The reimbursement decisions need to take into account the interest of the majority of the patients, the benefits of the new orphan drug versus the therapy in application if any, and the possibility to negotiate the pricing. Since the orphan drugs marketing authorisations approvals are handled through the centralised procedure, one should consider harmonising patients access to orphan drugs through all EU countries. As the pressure from high costs of orphan drugs will increase for health care systems, some measures on pricing are needed, maybe through the price negotiation with the industry, or also through new incentives to encourage generics for orphan drugs.

Total Pages: 54