Outcomes of Benefit Assessments

Orphan drugs with orphan designation (OD) are granted an added benefit by law in the German health technology assessment (HTA) process. However, some drugs indicated for rare diseases do not obtain or lose OD, leading to regular benefit assessments without orphan privilege. The objective of the current study is to investigate the outcomes of benefit assessments of orphan drugs without OD in Germany compared to non-orphan drugs and orphan drugs with OD.

Outcomes of 729 benefit assessments performed until March 2022 in Germany were analyzed regarding the granted added benefit, negotiated net rebate, and net annual therapy costs for orphan drugs without OD (n=114), non-orphan drugs (n=450), and orphan drugs with OD (n=165), respectively. Pair-wise comparisons were conducted to compare benefit assessment outcomes between orphan drugs without OD and non-orphan drugs as well as orphan drugs with OD, respectively.

Orphan drugs without OD were granted an added benefit equally frequently as non-orphan drugs (44.95% vs. 44.61%; p=0.95). Average net rebates did not differ significantly between orphan drugs without OD and non-orphan drugs (16.47% vs. 14.46%; p=0.66) or orphan drugs with OD (16.47% vs. 15.88%; p=0.51), respectively. However, significantly higher net annual therapy costs were achieved for orphan drugs without OD than for non-orphan drugs (mean: € 58,803 vs. € 22,963; p<0.001). Net annual therapy costs for orphan drugs with OD were dramatically higher than for orphan drugs without OD (mean: € 137,791 vs. € 58,803; p<0.001).

For orphan drugs without OD, no disadvantages in the AMNOG benefit assessment in Germany were identified compared to non-orphan drugs despite the usually higher difficulties in generating high-quality clinical evidence. The higher prices for orphan drugs even without OD may reflect a higher willingness to pay for conditions with a higher unmet medical need and risk in clinical development.