Original Title: Arzneimittel-Richtlinie/Anlage XII: Luspatercept (β-thalassämie)

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: Luspatercept is approved for adult patients with transfusion-dependent anaemia associated with Beta-thalassaemia. Benefit assessment is based on the multicentre, double-blind, randomized, placebo-controlled phase III trial ACE-536-B-THAL-001 (BELIEVE) to evaluate the safety and efficacy of luspatercept in patients with transfusion-dependent β-thalassemia. Overall, very few deaths occurred within the BELIEVE trial, one in the luspatercept + BSC arm and one in the placebo + BSC arm. Therefore, the effect of luspatercept on all-cause mortality cannot be estimated. There was a statistically significant negative effect of luspatercept (RR [95% CI] 4.08 [1.66; 10.02], p = 0.0005) on hospitalisation. The overall potential for bias for hospitalization is considered to be high, especially since bias due to regional differences in hospitalisation cannot be excluded in the multicentre study. Transfusion independence during any consecutive rolling interval for 24 weeks or more was achieved by 5 subjects in the luspatercept + BSC arm and none in the placebo + BSC arm. The number of responders is too small to estimate the effect. No statistically significant difference was found between the study arms regarding health-related quality of life measured by TranQoL and SF-36. Adverse events (AE) of NCI-CTCAE grade ≥ 3 (luspatercept + BSC: 31.4%, placebo + BSC: 17.4%, RR [95% CI] 1.80 [1.15; 2.83], p = 0.007), SAE (luspatercept + BSC: 16.6%, placebo + BSC: 7.3%; RR [95% CI] 2.26 [1.09; 4.69], p = 0.02) and AE that led to discontinuation of study medication (luspatercept + BSC: 6.7%, placebo + BSC: 0.9%, RR [95% CI] 7.32 [0.98; 54.57], p = 0.02), occurred statistically significantly more frequently in the luspatercept + BSC treatment arm than in the placebo + BSC treatment arm within the treatment and long-term treatment phases. The potential for bias for endpoints regarding AEs is considered to be low.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/574/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-4661/2021-01-21_AM-RL-XII_Luspatercept_D-560_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/574/#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/