[Pharmaceutical Directive/Annex XII: Glycerol phenylbutyrate (New Therapeutic Indication: Urea cycle disorders in infants aged 0 to < 2 months)]

The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)
Record ID 32018002144
English, German
Original Title: Arzneimittel-Richtlinie/Anlage XII: Glycerolphenylbutyrat (neues Anwendungsgebiet: Harnstoffzyklusstörungen bei Säuglingen von 0 bis < 2 Monaten)
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: Glycerolphenylbutyrate is an adjunctive drug for adult and pediatric patients aged ≥ 2 months with urea cycle disorders (UCD) that cannot be treated by dietary protein restriction and/or amino acid substitution alone. In addition to the pivotal study (cross-over RCT), seven supportive studies (single-arm observational studies) covering different age groups from the study program of the pharmaceutical company were included in the benefit assessment of Glycerolphenylbutyrate. The following endpoints were considered to be relevant to patients and therefore included in the benefit assessment: Mortality, number and severity of hyperammonemic crisis, quality of life (SF-36), safety. The unvalidated endpoint ammonia concentration in the blood was the primary endpoint of the RCT and therefore displayed but not considered in the benefit assessment. Risk of bias was considered to be low for the cross-over RCT but high for the single-arm studies. There were no deaths during the study period in any of the trials. During the study period, there was one patient in the control group and no patient in the intervention group in the pivotal trial who suffered from a hyperammonemic crisis. Data for quality of life were not available. Adverse events were more common in the intervention group, mainly due to gastrointestinal discomfort. There was one serious adverse event in each of the two treatment groups in the RCT. The duration of the pivotal trial was considered too short (4 weeks), especially because hyperammonemic crises are relatively rare when patients are compliant.
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
  • Urea Cycle Disorders, Inborn
  • Infant, Newborn, Diseases
  • Glycerol
  • Phenylbutyrates
  • Glycerol Phenylbutyrate
  • urea cycle disorders
  • inborn
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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