In the benefit assessment of orphan drugs (OD) the additional benefit (AB) is considered as proven with marketing authorization. However, if an OD has generated sales over 50-M-Euro with statutory health insurance within 12 months, the manufacturer is obliged to prove the AB against a comparative therapy. As a consequence of this re-assessment, the reimbursement price will be newly negotiated.

We analyzed all OD with sales having exceeded 50-M-Euro which therefore have undergone a re-assessment and a price negotiation (n=6). We used the decisions of the Federal Joint Committee and the official pharmacy prices. The calculation is based on ex-factoy price minus mandatory rebates.

In two cases, the category of AB was upgraded to “considerable”: Relevant for this was an improvement of morbidity and quality of life as well as the prolongation of overall survival in both cases. Surcharges of 14% and 6% were negotiated. Two procedures show inconsistent results with a partly deteriorated AB due to unsuitable data and a partly upgraded AB based on overall survival advantages. Additional rebates of 3% and 7% have been negotiated. For two OD the AB was downgraded to “no AB”: In one case there was a partial downgrading, which resulted in an additional rebate of 8%. In the other case the AB was completely downgraded due to unsuitable data. Here, the highest additional rebate of 17% is negotiated.

For the analyzed OD, the improved AB has resulted in a price surcharge on the previous reimbursement price. In oncology, the improvement of AB is mainly due to later data cut-offs. Also, it should be noted that in oncology, the comparator in the clinical study usually fulfils the criteria for the comparative therapy. The non-fulfilment of the comparative therapy is a risk in the re-assessment and results in a downgraded AB and additional rebates.