OBJECTIVES: To review the assessments of benefit for orphan drugs within the early benefit assessment process after implementation of AMNOG in Germany.  METHODS: Secondary research was used in this study. RESULTS: In contrast to other pharmaceuticals, by law, the benefit of orphan drugs (ODs) is proven by market authorization. No assessment vs. an appropriate comparator as defined by G-BA will be conducted, provided the revenue is less than 50 mio. EUR based on pharmacy retail prices including VAT over the past twelve months. IQWiG only assesses the accuracy of the number of patients and the therapy costs stated in the value dossier, while GB-A defines the extent of the benefit based on the Phase III data submitted with the abbreviated dossier. Seven ODs have been assessed by G-BA since implementation of AMNOG in 2011. Only one OD has received considerable benefit status in one patient subgroup, whilst two ODs have been classified as not quantifiable, and the other ODs assessed so far have been granted only a minor benefit. Prices have been negotiated for only 2 ODs so far: For Pirfenidon, with an unquantifiable benefit, a rebate of 11% was applied, while Tafamidis, with a minor benefit, received a rebate of 24.5%. CONCLUSIONS: There is a clear benefit for ODs (with annual sales of less than 50 mio EUR) in terms of reduced administrative burden and costs associated with the abbreviated value dossier submission. Furthermore, the OD status and the absence of a comparative added benefit assessment warrant a benefit score, whereas 60% of the non-orphan pharmaceuticals failed to prove an additional benefit vs. the defined comparator. As only two orphan drugs have completed price negotiations, it is very difficult to estimate, whether OD status will have a positive impact on future pricing opportunities after AMNOG.