OBJECTIVES

Certain conditions are so rare that it is not possible to collect comprehensive efficacy and safety data for new therapies. In these situations, or where it is unethical or unfeasible to collect such information, marketing authorization (MA) under exceptional circumstances (EC) may be a pathway to market approval in Europe. This study reviewed therapeutic medicines authorised under EC, and the subsequent health technology assessment (HTA) decisions made in England by the National Institute for Health and Care Excellence (NICE).

METHODS

Medicines currently licensed under EC were identified from the EMA website. Data on indication, orphan status, clinical trial design, and post-authorisation obligations were extracted from the European Public Assessment Reports. HTA decisions were identified from the NICE website.

RESULTS

Twenty-eight therapeutic products granted EC authorisation were identified. Five of these were withdrawn: three for commercial reasons by the marketing authorisation holder, one for being unable to provide the additional efficacy and safety data requested, and one for being unable to reproduce clinical efficacy in a further study. The majority were for treatment of genetic disorders (75%) or cancers (14%), and 82% of therapies were designated orphans at the time of MA. At least one randomized controlled trial was included in 54% (15/28) of authorisations as a pivotal clinical trial; 93% of these were placebo-controlled. NICE has appraised only 14% (4/28) of the therapies authorised through EC, all of which reached positive decisions, and all of which were for paediatric conditions.

CONCLUSIONS

The exceptional circumstances pathway provides an opportunity for the approval of drugs for which applicants cannot reasonably be expected to generate comprehensive efficacy and safety data, such as for very rare genetic disorders. Those drugs assessed by NICE have been approved for use, and several more have NICE guidance currently under development.