OBJECTIVES: Orphan drugs (ODs) have privileges in the early benefit assessment (EBA) and the subsequent price negotiation (PN) in Germany. The added benefit (AB) is acknowledged by law, no appropriate comparator therapy (ACT) is defined. If the sales of the OD exceed a sales volume threshold (SVT) of 30m€ (50m€ until Nov 2022), the product must undergo a regular EBA. The objective of this study was to update the analysis from 2023 (ISPOR Abstract HTA29).

METHODS: The results of all completed EBAs due to exceeding the SVT regardless the status of the PN by Mai 2024 were analyzed. The change of the AB (cAB) and respective reasons were determined using qualitative text analysis. The analysis of cAB was carried out at subpopulation level.

RESULTS: A total of 52 subpopulations were analysed. In 5 subpopulations, there was an increase/quantification of the AB due to the submission of new evidence, whereas in 2 subpopulations the AB was no longer quantifiable. In 13 subpopulations the AB remained the same despite the submission of new evidence in 7 cases, and in 32 subpopulations the extent of AB decreased. In case of a decrease of AB, a RCT of the assessed drug was often available in the orphan procedure. However, that comparison was not adequate for deriving an AB in the exceeding procedure due to short study duration or - compared to procedural demands in Germany - inadequate ACT.

CONCLUSIONS: The analysis showed again that there are several obstacles that arise when an OD is being faced with a regular EBA. The most common obstacle was the lack of AMNOG-eligible trials for a regular EBA. Pharmaceutical companies should consider a possible exceeding of the SVT and the resulting requirements when planning studies for AMNOG.