[Pharmaceutical Directive/Annex XII: Voretigene Neparvovec]

The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)
Record ID 32018002173
English, German
Original Title: Arzneimittel-​Richtlinie/Anlage XII: Voretigen Neparvovec
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: Voretigen Neparvovec is approved for the treatment of adult and pediatric patients with vision loss due to hereditary retinal dystrophy based on proven biallelic RPE65 mutations and who have sufficient viable retinal cells. The benefit assessment was based on the pivotal study 301, a randomized, multicenter, open-label study with study duration of one year. The investigational product (N=21) was compared to observational wait-and-see (N=10). Randomization was performed in a 2:1 ratio. Subjects in the control group could received the study medication after one year. Further details about the subsequent long-term follow-up study can be found in the amendment. Due to the open study design, the risk of bias was rated high for study 301. By end of the study one year after baseline, the Multi-Luminence-Mobility-Test showed a statistically significant result in favor of the intervention group (mean change intervention-control: 1,6 [95% KI: 0,7; 2,4]; p < 0.001). No person in the intervention group scored worse in the end of the study. Results on FST measured with white, blue and red light and Goldmann perimetry with stimulus III4e showed comparable statistically significant results in favor of the intervention. In the macular region but not in the fovea region, a statistically significant result in favor of the intervention was shown for Humphrey-perimetry. For visual acuity (ETDRS- and HOTV-vision chart) no statistically significant results were shown. All subjects in both treatment groups experienced at least one UE. Severe AEs, serious AEs, as reported in the study report, occurred only in the intervention group in three and two subjects, respectively, but not in the control group. Only AE ≥ grade 3 occurred in 55% in the intervention group and in 22% of patients in the control group but the results were not statistical significant. The RCT showed statistical significant changes in favor of the study drug in comparison to placebo in some efficacy endpoints.
Project Status: Completed
Year Published: 2019
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
  • Genetic Therapy
  • Retinal Dystrophies
  • cis-trans-Isomerases
  • Voretigene Neparvovec
  • Retinal Dystrophies
  • RPE65 mutation
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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