👉 German HTA requirements for indirect comparisons based on single-arm studies can hardly be fulfilled – repeated HTAs for Kymriah resulted in the same rating, despite significant improvements in the body of evidence

Kymriah (active substance: tisagenlecleucel) is a CAR-T cell therapy authorized for treatment of ALL, DLBCL and FL after prior therapies (authorized in August 2018 and April 2022). Pivotal trials are single-arm studies.

Kymriah is available in Germany.

🏆German HTA rating:

To date Kymriah was assessed in 7️⃣ German HTAs in 3️⃣ indications.

The HTAs for ALL and DLBCL were limited twice ❗ (HTA resolutions: March 2019 and September 2020). One of the reasons for limitations was the request for indirect comparisons. In the subsequent reassessments several additional studies were included for indirect comparisons, including patient-level data of RWE. However, in all HTAs the indirect comparisons were rejected by the German HTA body, e. g. because effects were too small, relevant confounders were missing, inclusion criteria of the studies were different or the eligibility of patients for CAR-T cell therapy was unclear. Overall, all HTAs resulted only in a non-quantifiable additional benefit because of the orphan drug status.

The HTA of the new indication FL also resulted in a non-quantifiable additional benefit (HTA resolution: December 2022). The reason for the limitation of this resolution was the ongoing RCT as part of the FDA requirements for accelerated marketing authorization. Results of this RCT also need to be submitted for German HTA.

💵 Launch price: € 320,000. Kymriah is used as a one-time treatment. Reimbursement price: € 239,000 (so far three price reductions, the price negotiations for the second reassessments in ALL and DLBCL are most likely not completed, yet). Current cumulated rebate: 25 %

📘 Special features of reimbursement:

Kymriah is reimbursed in Germany.

Kymriah was launched in September 2018 in Germany. From March 2019 on, the rebate contract coverage was 90 % and above. Interestingly, the rebate contracts were agreed on before the first reimbursement price was negotiated (first listed reimbursement price in October 2019). Like Yescarta, some of these rebate contracts are “pay for cure” contracts.

Kymriah is only reimbursed in hospitals, which meet all requirements of the ATMP Quality Assurance Guideline.

💡 HTA resolutions can be limited several times. Fulfilling all requirements for indirect comparisons based single-arm studies is hardly possible. Early rebate contracts may accelerate market entry.