OBJECTIVES: A specific feature of the German HTA process is the relevance of the orphan disease (OD) status. The additional medical benefit of orphan drugs, assessed by the German HTA body (G‑BA, Federal Joint Committee) is already acknowledged by approval. Companies are not obliged to present head-to-head data against an appropriate comparator. However, if the revenue per annum exceeds 50 million euros or OD status is lost, reevaluation against an appropriate comparator is mandatory. The aim of this study is to reveal the consequences of reevaluation with regard to acceptance of study data, patient relevant endpoints and extent of additional benefit assigned by G-BA and IQWiG (Institute for Quality and Efficiency in Health Care), respectively.

METHODS: A database containing all assessed AMNOG dossiers was screened for dossiers which have been assessed both under orphan and non-orphan conditions. Data on indication, size of target population, the comparator utilized in the company’s dossier, and outcome (added benefit) were collected and analyzed.

RESULTS: Since 2011, five former OD drugs were reassessed: ruxolitinib (hematology), pomalidomid, ibrutinib, ramucirumab (oncology), and macitentan (cardiovascular disorders). In four cases, annual revenues had exceeded 50 million euros, and one drug was deprived of the OD designation (ramucirumab). Time between reevaluation ranged from 14 months (ibrutinib) to 32.5 months (macicentan). At initial assessment all drugs obtained an added benefit. After full evaluation four of the five compounds retained an added benefit at least in parts of the population.

CONCLUSIONS: The transition from the assessment under OD to non-OD conditions pose a major challenge for companies as the existence of an added medical benefit is no longer preconditioned. Especially since clinical evidence for orphan diseases is limited, companies launching drugs likely to exceed the revenue limit or with uncertain OD status should be aware of the strict assessment criteria for non-orphan drugs.