Original Title: Arzneimittel-Richtlinie/Anlage XII: Migalastat (Neues Anwendungsgebiet: Morbus Fabry, 12 bis < 16 Jahre)

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: Migalastat (Galafold®) is indicated for long-term treatment of adults and adolescents aged 12 years and older with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency) and who have an amenable mutation. In accordance with the extension of approval, the present evaluation refers to patients with an age range of 12 to < 16 years. The benefit assessment is based on the pivotal study AT1001-020. This study is a single-arm, open-label phase IIIb trial in which 22 adolescents aged 12 to < 18 years and weighing ≥ 45 kg with diagnosis of Fabry disease and amenable (= migalastat-sensitive) GLA mutation are included. The two-stage study had a total study duration of 12 months. For the benefit assessment, only the relevant study population of subjects aged 12 to < 16 years at the time of study inclusion is considered (N = 15). There were no deaths in the study. Regarding morbidity, improvements were seen in nearly 50 % of the patients in the Patient Global Impression of Change for diarrhoea, abdominal pain, overall pain and activities of daily living. In the amendment of the benefit assessment the abdominal pain and fatigue subscales in both age-specific versions of the Fabry-specific Paediatric Health and Pain Questionnaire showed a slight improvement in scores in month 6 compared to baseline. Quality of life was assessed through the Paediatric Quality of Life Inventory (PedsQL). Both age-specific versions of the PedsQL total score, physical health summative score and psychosocial health summative score showed a slight improvement in health-related quality of life up to month 6 compared to baseline. 92,9 % of the patients experienced adverse events (AE) during treatment with migalastat. Severe AE were observed in 2 of 14 patients in the study and serious AE in 1 of 14 patients. In total, the potential for bias was assessed as high on the basis of the single-arm study design. The effect of migalastat on patient-relevant endpoints in the categories of mortality, morbidity, quality of life and side effects cannot be assessed due to the lack of a control group.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/729/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5285/2022-02-17_AM-RL-XII_Migalastat_D-727_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/729/#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/