Negotiating prices of drugs for rare diseases.

Abstract

Rare diseases are often serious, chronic and life-threatening. The European Union (EU) definition of a rare disease is one that affects fewer than 5 in 10 000 people. (1) At present, more than 6000 rare diseases are known; around 80% of them are genetic disorders and half of them occur during childhood. Grouped together, rare diseases affect 6-8% (or about 30 million people) out of the 508 million population of EU countries. (2) This roughly equals the estimated prevalence of diabetes in the World Health Organization European Region, which in 2013 was 6.8% of 658.7 million adults in the 20-79 year age group. (3) This illustrates the paradox of rarity: each disease is rare but collectively, rare diseases affect many people. (4) In 2009, responding to increasing concerns about the issue, the European Council published a recommendation (2009/C 151/02) on action in the field of rare diseases, recommending Member States to adopt and establish national plans for rare diseases by the end of 2013. (2) Rare diseases are associated with a high psychological burden for the patient but they can also have a major impact on a patient's family. (5) In addition to the health burden on patients, few of these diseases have an effective drug treatment available. This is because the drugs to treat rare diseases (called orphan drugs) are not commercially viable for pharmaceutical companies, due to the small number of patients per disease. To encourage pharmaceutical companies to develop and market orphan drugs, the European Parliament and the European Council published the regulation (EC) No 141/2000 on orphan medicinal products in 1999. (1) Orphan designation for a medicine is granted at the European level by the European Medicines Agency (EMA). Three criteria must be met, as stated in the regulation: (i) the medicine must be intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating; (ii) the prevalence of the condition in the European Union must be no more than 5 in 10 000 or it must be unlikely that the marketing of the medicine would generate sufficient returns to justify the investment needed for its development; and (iii) no satisfactory method of diagnosis, prevention or treatment of the condition concerned can be authorized, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition. (1) The application for orphan designation, which can be submitted by the sponsor of the medicinal product at any stage of drug development, is then examined within 90 days by the Committee for Orphan Medicinal Products of the EMA. When a medicine is granted orphan designation, several incentives are provided to the sponsor of a clinical trial, as stated in regulation (EC) No 141/2000. (1) These incentives include protocol assistance, scientific advice from EMA before the submission for marketing authorization and market exclusivity of 10 years once the medicine is marketed. This period of market exclusivity can be extended by two years for medicines that comply with an agreed investigation plan for medicines for paediatric care. Finally, depending on the status of the sponsor and the type of service required, reductions in fees to be paid for regulatory activities related to the evaluation of orphan medicinal products by EMA (e.g. protocol assistance, application for marketing authorization) can also be available for the sponsor. By the end of 2015, 89 different orphan medicinal products had received authorization to enter the market from the EMA's Committee for Medicinal Products for Human Use, and 123 other medicinal products intended for rare diseases but without the orphan designation in Europe also received the European marketing authorization. (6) In addition, an increasing number of applications for orphan designation are submitted to EMA each year (Fig. 1). (7) As a consequence, an increasing number of applications for a marketing authorization of an orphan medicinal product is observed each year. …