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 determine the change of the AB (cAB) and respective reasons after exceeding the SVT.

METHODS: The results of all completed EBAs due to exceeding the SVT regardless the status of the PN by March 2023 were analyzed. The cAB and respective reasons were determined using qualitative text analysis. The analysis of cAB was carried out at subpopulation level.

RESULTS: A total of 39 subpopulations were analyzed. 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 11 subpopulations the AB remained the same despite the submission of new evidence in 2 cases, and in 21 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 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. The in most cases available RCT were often not suitable because the ACT was not adequately implemented. Pharmaceutical companies should consider a possible exceeding of the SVT and the resulting requirements when planning pivotal studies.