Original Title: Arzneimittel-Richtlinie/Anlage XII: Lumasiran (Hyperoxalurie)

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: Lumasiran (Oxlumo®) is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in all age groups. The benefit assessment is based on the pivotal studies ILLUMINATE-A and ILLUMINATE-B. ILLUMINATE-A is a multinational, double-blind phase III study evaluating the efficacy and safety of lumasiran in adults and children (≥ 6 years of age) with a documented diagnosis of PH1 and relatively well-preserved renal function. The study population included 39 subjects randomised in a 2:1 ratio to lumasiran vs. placebo. Treatment phase lasted 6 months. ILLUMINATE-B is a single-arm, open-label, multinational phase III study evaluating the efficacy, safety, pharmacodynamics and pharmacokinetics of lumasiran in pediatric patients (< 6 years of age) with a documented diagnosis of PH1 and relatively well-preserved renal function. Treatment phase lasted 6 months. The data cut included 18 subjects treated with lumasiran who had completed the visit at study month 6. Primary endpoint of both studies was the percent change in 24h urinary oxalate concentration at 6 months compared to baseline. There were no deaths in the studies. Regarding morbidity, the amendment showed no statistically significant differences between study arms from baseline to month 6 in the general health status using EQ-5D-VAS for ILLUMINATE-A. ILLUMINATE-B showed little or no change in age-adjusted anthropometric parameters of body length and weight. Quality of life was only assessed in ILLUMINATE-A through the PedsQL and KDQOL-36. Both scales did not show statistically significant differences between study arms up to month 6 compared to baseline. In ILLUMINATE-A, 84.6% patients in the lumasiran arm and 69.2% in the placebo arm experienced at least one adverse event (AE) during the 6-month double-blinded treatment phase. No severe AEs, serious AEs or AEs of clinical interest occurred during the 6 months of treatment. For ILLUMINATE-B, safety events during therapy with lumasiran were limited to AEs of mild and/or moderate severity.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/639/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-4910/2021-07-01_AM-RL-XII_Lumasiran_D-622_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/639/#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/