Original Title: Arzneimittel-Richtlinie/Anlage XII: Setmelanotid (Neues Anwendungsgebiet: Adipositas und Kontrolle von Hunger, Bardet-Biedl-Syndrom, ≥ 6 Jahre)

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: Setmelanotid (Imcivree) is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed Bardet Biedl syndrome (BBS) in adults and children 6 years of age and above. The benefit assessment is based on the „RM-493-023“ trial with a 14-week RCT and an 52 weeks open-label follow-up. A patient received in 52 weeks of treatment in total. The total observation time was 66 weeks. After being randomized in the RCT control arm, the patient will receive 52 weeks of treatment and the intervention arm will continue to receive the intervention for 38 weeks. The study included patients with BBS and Alstroem-syndrom. As the approval only covers BBS patients, the benefit assessment is about the BBS-population. The primary objective of the trial was the portion of patients with a weight loss ≥10% at week 52 compared to the patients own baseline. Furthermore, the study aimed the change in hunger measured with the „daily hunger questionnaire“ which had major limitations in the operationalization and have only been used in patients without cognitive impairments. The bias potential was considered high due to the short RCT duration and side effects which potentially affected the blinding. Additionally, the statistical analysis procedure was unclear. In total 29 patients were randomized into the pivotal cohort. In the RCT phase 14 patients were randomized into the intervention arm and 15 into the controlarm. The mean difference in weightloss in kg was -3.81 kg [-7.03; -0.53] in favor for the intervention arm compared to the control group. The mean weight per patient (n=29) was 107.13 kg (min: 54.3 kg; max: 174,8 kg) at baseline. After 52 weeks the mean reduction in weight (kg) was 9.03 kg (min: -27,7.5 kg). The most reported adverse event in the RCT was the hyperpigmentation of the skin (59.1%). In summary, the trial design and the reporting of the results were assessed as inadequate. The clinical relevance of loosing weight in BBS patients, who are often comorbid, is unclear.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/959/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-6263/2023-11-02_AM-RL-XII_Setmelanotide_D-941_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/959/#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/