Background: In the EU alone, about 30 million people are affected by more than 6000 different rare diseases, thus representing a major public health issue. The development of drugs for rare diseases (orphan drugs) used to be commercially less attractive due to small markets, resulting in huge unmet medical needs in affected patients. This led to legislation to incentivise orphan drug development, such as the EU Orphan Regulation of 2000. Since then, there has been a sharp increase in the number of orphan drugs approved in the EU.
Objectives: To assess whether the increase in orphan drug approvals has led to an evidence based improvement in patient relevant outcomes for a relevant number of patients with rare diseases.
Methods: Results of health technology assessments (HTAs) of orphan drugs in Germany were analysed to determine the frequency of an added benefit (i.e. an improvement in patient relevant outcomes) compared to the standard of care. The evidence underlying these assessments was examined. Clustering of orphan drugs in certain therapeutic indications was evaluated by comparing approved indications with all known rare diseases.
Results: No proof of added benefit was shown for 54% of the research questions on orphan drugs. This was mostly due to the lack of robust evidence compared to the standard of care. If there was a high unmet medical need in an indication, an added benefit was twice as likely. Clustering of orphan drugs was evident in oncology.
Conclusions: Major evidence gaps exist for many orphan drugs, hampering informed treatment decisions by patients and doctors, potentially resulting in suboptimal care. While there are clusters of orphan drugs in some therapeutic indications, a large number of patients with rare diseases remain without adequate treatment options. Therefore, orphan drug regulations need to be reformed to improve the generation of robust evidence in comparison with the standard of care and guide research to indications with the highest unmet medical needs outside of existing clusters. Patient involvement: Patient representatives are regularly involved in German HTAs in an advisory capacity. Their opinions are taken into account for decisions on the added benefit of orphan drugs.