Original Title: Arzneimittel-Richtlinie/Anlage XII: Volanesorsen

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: Volanesorsen is approved as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome (FCS) and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate. Benefit assessment of volanesorsen is based on the pivotal APPROACH trial (CS6). The study was a randomized, double-blind, multicenter, placebo-controlled phase III trial in a parallel-group design with a screening phase of up to 8 weeks (run-in phase), a treatment phase of 52 weeks, and a subsequent follow-up phase of 13 weeks or a switch to the open-label, single-arm, long-term APPROACH OLE study (CS7) with up to one year of treatment. No deaths occurred during the trial. The endpoints "change in health status based on EQ-5D-VAS" and "independently confirmed acute pancreatitis" are used for the benefit assessment regarding morbidity. Differences in change in "EQ-5D-VAS" between baseline and week 13 between study arms were not statistically significant. Precise and reliable and therefore meaningful results were not achievable for the endpoint "independently confirmed acute pancreatitis” due to the overall small number of events. Health-related quality of life was assessed with the generic quality of life questionnaire SF-36. There were no statistically significant differences between the study arms related to SF-36 summary scales MCS and PCS. A comparable number of subjects developed adverse events (AE) during the 52-week treatment week under volanesorsen and placebo (97.0 vs. 93.9%). There were 9 subjects (27.3%) in the volanesorsen arm and none in the placebo arm in whom AE led to treatment discontinuation. No appropriate effect estimates to assess the safety endpoints that consider the different treatment duration in the two study arms were provided. The potential for bias in the analyses of all endpoint assessed was considered to be high.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/479/#english

Year Published: 2020

URL for published report: https://www.g-ba.de/downloads/39-1464-4178/2020-02-20_AM-RL-XII_Volanesorsen_D-469_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/479/#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/