OBJECTIVES

In Germany, the additional benefit (AB) of orphan drugs with annual sales below €50 mn is deemed proven by the marketing authorization. The G-BA determines only the extent of AB, from abbreviated submissions. However, when annual sales exceed €50 mn, a re-assessment is triggered, requiring a full submission followed by price re-negotiations with the GKV-Spitzenverband.

Relatively costly orphan drugs, such as tisagenlecleucel and axicabtagene ciloleucel (both initially assigned a non-quantifiable AB), may rapidly exceed the threshold, with limited time for longer-term or additional data to emerge for a re-submission. To understand the challenges for such products, we evaluated the impact of re-assessments on the AB rating and drug price.

METHODS

We reviewed all 71 orphan product G-BA assessments conducted before 2 May 2019. Launch and negotiated reimbursed prices were retrieved from Lauer Taxe.

RESULTS

Only eight products (≈11%) have been re-assessed, two with approvals based on single-arm trials. The overall AB rating improved for daratumumab in combination from non-quantifiable to considerable, based on a new comparative study, but worsened for ibrutinib as the new indirect treatment comparison (ITC) was not accepted.

For the remaining products, ratings improved for carfilzomib and ruxolitinib, based on longer-term OS data. The overall AB rating was unchanged for pomalidomide and worsened for macitentan, as a non-G-BA-defined comparator was chosen. Re-assessments of ivacaftor and nintedanib are ongoing. No clear correlation was seen between the change in price (+5% to -21%) and AB.

CONCLUSIONS

Re-assessments of products initially assessed with single-arm studies required a comparative study or acceptable ITC to maintain an AB. However, the AB rating is only one factor in price negotiations. With multiple costly one-off orphan treatments in development, re-assessments are expected to become more frequent. Future CAR-T re-assessments may provide good case studies to understand evidence generation activities to support re-assessment and pricing for high-cost agents.