Original Title: Arzneimittel-Richtlinie/Anlage XII: Amikacin (Mycobakterium-avium-Komplex-Lungeninfektionen)

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: Amikacin (liposomal) is approved for the treatment of non-tuberculous mycobacterial (NTM) lung infections caused by Mycobacterium avium Complex (MAC) in adults with limited treatment options who do not have cystic fibrosis. Benefit assessment is based on the randomised, open-label, multicentre CONVERT trial on the safety and efficacy of liposomal amikacin for inhalation (ALIS) as an add-on to combination antibiotic therapy (MDR) compared to MDR alone in adult patients with pulmonary MAC infection without cystic fibrosis. In the CONVERT trial, 4.9% of the intervention group and 7.1% of the control group died during the entire study period. The statistical analysis of overall survival is considered to be biased to such an extent that the effect estimates are not considered for benefit assessment, because of informative censoring within study month 8. 16 % of the intervention group and 0 % of the control group were culture negative 3 month off treatment for 12 months after culture conversion. For two (EQ-5D-3L VAS, hospitalisation) out of three patient-relevant morbidity endpoints, no sufficient statistical analyses were provided. No statistically significant difference in 6-minute walking distance was observed. At month 6, a statistically significant worsening of the St George's Respiratory Questionnaire total score (LSM difference [95% CI] = 3.16 [0.08; 6.23], p = 0.04) and activity domain score (LSM difference [95% CI] = 4.05 [0.18; 7.92], p = 0.04) was observed. Due to the difference of > 15% in the proportion of missing values and the open study design, the results are considered highly biased. AEs of NCI-CTCAE grade ≥ 3 and AEs leading to study discontinuation occurred more frequently under treatment with ALIS+MDR than under MDR alone. The potential for bias in all safety endpoints was assessed to be high due to the open study design.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/612/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-4842/2021-05-20_AM-RL-XII_Amikacin_D-600_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/612/#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/