Although orphan drug (OD) development is challenging, incentives have enabled a diversity to achieve EMA, typically from manufacturers of a single OD with a single indication. Rare oncology (RO) approval is frequently supported by a single, large, pivotal RCT often open-labelled with active control. In contrast, rare disease (RD) have multiple, smaller studies often double-blinded with placebo. Conditional EMA is more common for RO whereas exceptional EMA is more common for RD.
Conditional EMA often occurred for RO with ongoing phase-three pivotal studies. In the absence of ongoing studies for RD, exceptional EMA was often granted with the requirement to establish a registry. This review demonstrates a flexible, diverse approach to the evidence and regulatory approval of ODs, with stark differences between RO and RD. Subsequent assessment of the evidence for access should adopt a bespoke approach with a framework beyond standard quality criteria.
