Original Title: Arzneimittel-Richtlinie/Anlage XII: Cerliponase alfa - Neubewertung nach Fristablauf (Neuronale Ceroid-Lipofuszinose Typ 2)

Authors' objectives: The Federal Joint Committee [Gemeinsamer Bundesausschuss (G-BA)] has had the legal task of carrying out an (additional) benefit assessment for all newly approved drugs with new active ingredients immediately after market entry (§ 35a SGB V). The result of this assessment is the basis for deciding how much the statutory health insurance pays for a new drug with a new active ingredient. The G-BA was commissioned to carry out the benefit assessment through the Pharmaceuticals Market Reorganisation Act [Gesetz zur Neuordnung des Arzneimittelmarktes (AMNOG)]. In the context of the early benefit assessment of medicinal products containing new active substances, the following rules apply to orphan drugs: According to the legal requirements (§ 35a SGB V), the additional medical benefit of these drugs is already considered to be proven by the approval. The G-BA determines the extent of the additional benefit for orphan drugs that do not exceed a turnover of 50 million Euros in the last twelve calendar months, on the basis of the approval and the studies justifying the approval.

Authors' results and conclusions: Cerliponase alfa, Brineura® is indicated for the treatment of neuronal ceroid lipofuscinosis type 2 disease, also known as tripeptidyl peptidase 1 deficiency. For re-evaluation, the pharmaceutical company submitted results of the intervention studies 190-201/202 and 190-203, the European registry study 190-504 and of the German registry DEM-CHILD-RX. Data of indirect comparisons for studies 190-201/202, 203 and DEM-CHILD RX were also submitted. However, only the results of the studies 190-201/202 und 190-203 were presented in the benefit assessment report. Study 190-201/202 was a phase 1 /2 multi-center, open-label, single arm study in 23 patients between 3-15 years with a ML (“motor” / “language”) score between 3-6 (Score –Range: 0-6). Study 190-203 was a phase 2, multi-center, open-label, single arm study in 14 patients <18 years with ML score between 3-6. Intra-individual comparison showed higher decline in motor and language skills in study 190-201/202 on week 281 than in study 190-203 on week 145 (mean decline by 1.2 (SD 0.9) vs -0.4 (0.9)). In study 190-201/202, decrease in quality of life, measured by PedsQL, was shown in some domains. No deaths occurred in both studies. (Serious) adverse events were observed frequently in both studies. A comparison, based on external controls, was considered not appropriate because of non-systematic selection of confounders, limited information regarding the external control (e.g., patient characteristics, concomitant medication), generalizability, limited information regarding birth dates leading to bias regarding changes in treatment and diagnostic criteria over time. The results of the indirect comparison for both studies were presented in the appendix of the report. In both studies the analysis showed pronounced effects in favor of the intervention for overall survival and disease progression, measured by the ML-score. However, the mentioned limitations have to be considered.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/843/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5775/2022-12-15_AM-RL-XII_Cerliponase-Alfa_D-849_EN.pdf

Requestor: The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/843/#nutzenbewertung

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Germany

Organisation Name: The Federal Joint Committee

Contact Address: Gutenbergstr. 13, 10587 Berlin, Germany

Contact Name: Fachberatung Medizin [Department of Medical Consultancy]

Contact Email: Fachberatung-Medizin@g-ba.de

Copyright: https://www.g-ba.de/sys/impressum/