Original Title: Arzneimittel-Richtlinie/Anlage XII: Ixazomib (Neubewertung nach Fristablauf: Multiples Myelom, mind. 1 Vortherapie, Kombination mit Lenalidomid und Dexamethason)

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: Ixazomib (NINLARO®), in combination with Lenalidomide and Dexamethasone (LenDex), is approved for the treatment of adults with multiple myeloma (MM) who have received at least one prior therapy. The benefit assessment of Ixazomib is based on the pivotal study C16010, a randomized, double-blind, controlled, multicenter phase III study in which adults with relapsed and/or refractory MM who had received 1-3 prior therapies were randomized in a 1:1 ratio to either Ixazomib/LenDex (N = 360) or placebo/LenDex (N = 362). Given a low risk of bias (RoB), there was no statistically significant difference between treatment groups for the endpoint "overall survival." Regarding morbidity, there were no statistically significant differences between treatment groups for the endpoints "pain" (measured by BPI-SF [Brief Pain Inventory - Short Form]) and "health status" (measured by EQ-5D VAS [European Quality of Life – 5 Dimensions Visual Analogue Scale]). There was a statistically significant difference in favor of Ixazomib/LenDex for the single-item scale "appetite loss" of the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire – Core 30). For other scales of the EORTC QLQ-C30 and for domains of the EORTC QLQ-MY20 (EORTC QLQ – Multiple Myeloma 20), there were no statistically significant differences. Regarding quality of life, there was a statistically significant difference in favor of Ixazomib/LenDex for the domain "future perspective" (EORTC QLQ-MY20) and a statistically significant difference to the disadvantage of Ixazomib/LenDex for "global health status/QoL" (EORTC QLQ-C30.) There is a high RoB for all endpoints of the categories morbidity and quality of life, among others, due to a markedly decreasing response rate during the course of the study. Given a low RoB, there were no statistically significant differences between the treatment groups for severe or serious adverse events and treatment discontinuations due to adverse events.

Authors' identified further research: Ixazomib, Multiple Myeloma, Kahler disease, Plasma cell myeloma, myelomatosis,

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/751/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5385/2022-04-21_AM-RL-XII_Ixazomib_D-753_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/751/#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/