👉For the first time, the arbitration board was faced with the complex task to develop criteria for the monetary evaluation of the one-time therapy Zynteglo, which promises to replace a long-term therapy.

Zynteglo (active substance: betibeglogene autotemce) is a gene therapy for treatment of transfusion-dependent β-thalassaemia (TDT). Authorization in May 2019 was based on 4 single-arm trials in which 32 patients were treated with Zynteglo.

As reimbursement price negotiations in Germany did not result in an adequate price, Zynteglo was withdrawn from the German market in April 2021. Eventually the marketing authorization of Zynteglo was withdrawn in March 2022 for commercial reasons. Consequently, Zynteglo is no longer available in Germany.

🏆German HTA rating:

No direct comparative data for Zynteglo exists. Accordingly, The German HTA rating in May 2020 resulted in a non-quantifiable additional benefit, only because of the orphan drug status. However, the German HTA body admits that data on transfusion independence clearly demonstrates a significant benefit in comparison to the natural course of TDT.

The resolution was limited until May 2025, to allow reassessment of final results of ongoing studies and new long-term data. This was in line with the conditions imposed by the EMA.

💵 Launch price: € 1,575,000. Zynteglo is a one-time treatment. Reimbursement price: € 629,974. Rebate: 60 %.

The reimbursement price was set by the arbitration board and calculated in a complex way: Annual costs of the current long-term infusion therapy for TDT (~ € 40,000) were multiplied by the expected transfusion independence (15 years), afterwards a premium was added for the additional benefit. This resulted in the “success price” of € 787,467. However, as only 80 % of the patients were transfusion independent in the clinical trials, the “success price” was reduced to 80 % resulting in the “interim price” of € 629,974. By providing promising RWE on efficacy, the reimbursement price could have been increased up to the “success price”.

📘 Special features of reimbursement:

From June 2020 on Zynteglo had a rebate contact coverage of above 90 %. One feature of these rebate contacts was the result-oriented risk distribution. Therefore, the reimbursement was linked to clinical outcomes (e. g. absence of blood transfusions) and reimbursement was distributed over five installments: Initial installment and 4 annual outcome-based installments of € 315,000 each.

💡 Right after launch, health insurances agreed to set up risk-sharing agreements for Zynteglo. After failed reimbursement price negotiation, the arbitration board developed a multi-year perspective in the monetization of the additional benefit and a result-oriented reimbursement price adjustment. While planning such early (risk-sharing) rebate contracts for a single-use ATMP to accelerate market entry in Germany, the narrative of Zynteglo provides valuable insights for planning the Market Access strategy.