Original Title: Crizanlizumab (Prävention vasookklusiver Krisen bei Sichelzellkrankheit)

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: Crizanlizumab (CRI) is approved for the prevention of recurrent vaso-occlusive crises (VOC) in patients aged ≥ 16 years with sickle cell disease (SCD). The benefit assessment of CRI is based on the pivotal SUSTAIN study, which is a randomised, multicentre, double-blind, placebo-controlled phase II trial to evaluate the efficacy and safety of two doses of CRI. The trial compared CRI with or without hydroxyurea (HU) versus placebo with or without HU in patients 16-65 years of age with SCD and with 2-10 VOC during the previous 12 months. An effect of CRI versus placebo was reported for the annual rate of VOC in the primary analysis. A clear interpretation of the result does not seem possible due to multiple limitations. More adequate sensitivity analyses indicate a consistent direction of effect, but the 95% CIs of each of these analyses include 1. Due to extensive limitations resulting from the operationalisation, the high amount of study discontinuations, the missing values, the analysis procedure and potential outcome-driven reporting, the results on morbidity are highly biased. Two deaths per arm were reported descriptively. Valid statements on the effect of CRI on overall survival seem not possible. The 36-item Short Form Health Survey was used to assess quality of life. Due to selective reporting and methodological limitations of the evaluations presented, the results were not directly used for the benefit assessment. The safety data indicate a mostly balanced safety profile of CRI compared to placebo, however with limitations and a high risk of bias. Statistically significant results to the disadvantage of CRI were only reported for the system organ class "Injury, poisoning and complications caused by interventions" as an adverse event with an incidence of ≥ 10 %. The safety data appears to be of preliminary nature, among other things due to the short study duration. The STAND study could lead to more reliable statements on the safety profile of CRI.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/614/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-4844/2021-05-20_AM-RL-XII_Crizanlizumab_D-591_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/614/#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/