[Pharmaceutical Directive/Annex XII: Atidarsagen autotemcel (metachromatic leukodystrophy with biallelic mutation in the ARSA gene)]

The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)
Record ID 32018001747
English, German
Original Title: Arzneimittel-Richtlinie/Anlage XII: Atidarsagen autotemcel (metachromatische leukodystrophie mit biallelischer mutation im ARSA-Gen)
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: Libmeldy® is used for treatment of metachromatic leukodystrophy (MLD), characterised by biallelic mutations in the arylsulfatase A (ARSA) gene leading to a reduction of the ARSA enzymatic activity: in children with late infantile or early juvenile forms, without clinical manifestations of the disease; in children with the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline The benefit assessment is based on an integrated data set (IDS) including four pivotal studies: 201222, CUP 207394, CUP 20658 and HE 205029. Study 201222 is a phase I/II, non-randomised, open-label, prospective, single-arm, monocentric study of children with LI- or EJ-MLD to determine the efficacy and safety of Libmeldy®. CUP 207394 is a case report of a child with early symptomatic EJ-MLD treated with Libmeldy® in a compassionate use program (CUP). CUP 206258 was a case series of presymptomatic patients with early-onset LI and EJ MLD treated with Libmeldy®. Study HE 205029 is a case series of patients with LI-MLD treated with Libmeldy® under Hospital Exemption. The IDS included data on 30 patients with LI, intermediate, and EJ MLD from studies 201222 (n = 21), CUP 207394 (n = 1), CUP 206258 (n = 5) and HE 205029 (n = 3). Median age at inclusion was 14 months (min; max: 7; 136). Based on the absence of a valid comparison, the available observation periods to date and the limited number of patients treated with Libmeldy®, no conclusions could be drawn regarding mortality, morbidity and safety. 2 and 3 years after Libmeldy® infusion, patients did not have worse gross motor function compared with baseline. However, these results are subject to uncertainties. Due to the limited observation durations in the studies and the small number of subjects treated, a conclusive assessment of safety was not possible.
Project Status: Completed
Year Published: 2021
Requestor: The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Germany
MeSH Terms
  • Leukodystrophy, Metachromatic
  • Child
  • Young Adult
  • Adolescent
  • Genetic Therapy
  • Atidarsagen autotemcel
  • metachromatic leukodystrophy
  • OTL-200
  • Hematopoietic Stem Cells
  • Leukodystrophy
  • biallelic mutations
  • arysulfatase A
  • ARSA gene
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/
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