Original Title: Arzneimittel-Richtlinie/Anlage XII: Olipudase alfa (Mangel an saurer Sphingomyelinase (ASMD) Typ A/B oder Typ B)

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: Olipudase alfa (Xenpozyme®) is indicated as an enzyme replacement therapy for the treatment of non-Central Nervous System (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD) in paediatric and adult patients with type A/B or type B. The benefit assessment is based on the pivotal studies ASCEND and ASCEND-Peds. ASCEND is a randomized, placebo-controlled, double-blind Phase II/III study evaluating the efficacy and safety of olipudase alfa in adults with a documented diagnosis of ASMD type B (N=36) for 52 weeks. The Study ASCEND-Peds is a Phase I/II, open-label, single-arm study evaluating the efficacy and safety of olipudase alfa in pediatric patients aged <18 years with non-neuronopathic ASMD (N=20) for 64 weeks. No deaths occurred in both of the studies. For the endpoints morbidity (fatigue [BFI item 3], pain [BPI item 3], visual analogue scale of the EQ-5D questionnaire, Patient Global Impression of Symptom Severity) and quality of life (SF-36), no statistically significant differences were found between the treatment-arms in the ASCEND study. In the ASCEND-Peds study, there was a statistically significant increase on the PedsQL Multidimensional Fatigue Scale and a statistically significant reduction on the PedsQL Pediatric Pain Questionnaire. With regard to the endpoint quality of life, statistically significant increases were found in the ‘Physical health’ and ‘Psychosocial health’ domains of the patient-reported PedsQL core module. Considering the safety endpoint, there were no statistically significant differences in the occurrence of severe adverse events (AE), serious AE (SAE) and treatment discontinuations due to AEs between the study arms of the ASCEND study. Within the ASCEND-Peds study, 3 severe AEs (15,0%) and 5 SAEs (25,0%) occurred. In addition to the small sample size of the ASCEND-Peds study a comparative assessment of efficacy and safety is not possible due to the lack of a control group.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/882/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-5913/2023-03-16_AM-RL-XII_Olipudase-alfa_D-869_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/882/#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/