Original Title: Arzneimittel-Richtlinie/Anlage XII: Odevixibat (progressive familiäre intrahepatische Cholestase)

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: Odevixibat (Bylvay®) is used in the treatment of progressive familial intrahepatic cholestasis (PFIC) in patients aged 6 months or older. The benefit assessment of Odevixibat is based on the pivotal study PEDFIC1 (A4250-005) and the supportive study PEDFIC2 (A4250-008). PEDFIC1 is a randomized, double-blind, placebo-controlled, multicentre phase III study that investigates the efficacy and safety of Odevixibat vs. placebo in children and adolescents (6 months to 18 years) with PFIC type 1 and type 2. The study population included 62 participants randomized in a 1:1:1 ratio stratified by PFIC subtype and age into the treatment arms Odevixibat 40 μg/kg/day, 120 μg/kg/day or placebo. Treatment duration lasted 24 weeks and after that, subjects were eligible to participate in the extension study PEDFIC2 with administration of the maximum dose of 120 μg/kg/day, lasting 72 weeks. Additionally, in a second cohort further patients of any age with PFIC of any type could be included in PEDFIC2, bringing the number of participants to a total of 71 at the interim datacut (20 Juli 2020). There were no deaths in the studies. Odevixibat showed statistically significant advantages over placebo in pruritus recorded via patient-diary with unclear potential for bias due to no information on missing data. Surgical interventions (biliary diversion, liver transplantation) were not performed in PEDFIC1 and did occur rarely in PEDFIC2. No differences occurred between study arms in growth parameters height, weight and BMI and due to invalid analysis the results on Patient Global Impression of Symptoms and -Change were not taken into account. Quality of life, measured by the PedsQL, was not considered because of high rates of missing data and missing of separate analysis of proxy data. There were no relevant differences between study arms in adverse events, however data on safety is limited by small patient numbers and a short follow-up period.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/739/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5313/2022-03-03_AM-RL-XII_Odevixibat_D-725_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/739/#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/