ATMPs in Germany - Upstaza®

👉 For HTA on Upstaza, indirect comparisons were worth the effort ‒ positive statements by the HTA body on the results of the indirect comparisons might help during price negotiation or arbitration

Upstaza (active substance: eladocagene exuparvovec) is a gene therapy that expresses L-amino acid decarboxylase enzyme (hAADC). It was authorized for treatment of patients with aromatic L-amino acid decarboxylase (AADC) deficiency in July 2022. In three single arm studies (AADC-010, AADC-011, AADC-1601), 21 patients were treated with Upstaza. Upstaza is available in Germany.

🏆German HTA rating:

No direct comparative data for Upstaza exists. Accordingly, The German HTA rating in February 2023 resulted in a non-quantifiable additional benefit. Unlike assessment results of other orphan drugs, the additional benefit is “real” and is based on the submitted evidence. Compared to the natural disease progression, Upstaza showed “dramatic effects” in the milestone analysis (endpoints “achieving full head control” and “sitting unassisted”). 

The HTA resolution is limited until February 2028. Currently, a registry study collects comparative RWE for Upstaza. The German HTA body wishes to reassess Upstaza on basis of this new data.

💵 Launch price: € 3,500,000. Upstaza is a one-time treatment. Reimbursement price: € 3,000,000. Rebate: 14 %

Upstaza was temporarily withdrawn from the German market (August 2023 to March 2024), before the reimbursement price was listed – reasons for the withdrawal may be many and varied.

📘 Special features of reimbursement:

Upstaza is only reimbursed in hospitals, which meet all requirements of the ATMP Quality Assurance Guideline. The requirements for Upstaza in AADC deficiency just came into effect in September 2024.

💡Indirect comparisons on basis of single arm trials usually not allow quantification of an addition benefit. However, to prepare for price negotiation or arbitration in the best possible way, indirect comparisons should always be considered in the overall HTA strategy.