Original Title: Arzneimittel-​​​Richtlinie/Anlage XII: Pegvaliase

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: Pegvaliase is approved for the treatment of patients aged 16 years and older with phenylketonuria whose blood phenylalanine levels are not adequately controlled (blood phenylalanine levels greater than 600 µmol/l) despite prior use of available treatment options. The benefit assessment of pegvaliase is based on the pivotal studies 165-301 and 165-302. 165-301 is a randomized phase III study comparing different doses of pegvaliase. Solely the total study population, but no comparison of different doses, is used for the benefit assessment. 165-302 is a phase III study consisting of four different study periods. Solely study periods 2 (randomized, double-blind discontinuation) and 4 (non-blinded long-term extension) are relevant for the current benefit assessment. One death from electrocution with no association to study drug was reported in 165-301. No death was reported in 165-302. The endpoints "POMS," "PKU-POMS," and "ADHD-RS-IV" are not considered in this benefit assessment due to substantial uncertainties regarding validity. The endpoint "phenylalanine concentration in blood" is a clinically relevant laboratory parameter for diagnosis and therapy management, however, it is not directly relevant for patients. No data were collected on health-related quality of life. Based on the available data, it is not possible to make a valid statement on the relative efficacy of pegvaliase in terms of patient-relevant outcomes. The number of patients with at least one adverse event during the entire treatment with pegvaliase cannot be reproduced. Controlled data against placebo are available for a short period of 8-weeks. However, there are no effect estimates and p-values. Moreover, only patients who had previously received pegvaliase and completed one of the prior studies were included in this analysis. Therefore, based on the available data, it is not possible to make a valid statement regarding the long-term safety of pegvaliase compared to other treatment options.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/471/#english

Year Published: 2019

URL for published report: https://www.g-ba.de/downloads/39-1464-4086/2019-12-19_AM-RL-XII_Pegvaliase_D-467_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/471/#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/