Original Title: Arzneimittel-Richtlinie/Anlage XII: Setmelanotid (Adipositas und Kontrolle von Hunger, POMC-, PCSK1- oder LEPR-Mangel-Adipositas, ≥ 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: Setmelanotide is approved for adults and children 6 years of age and older for the treatment of obesity and the control of hunger associated with genetically confirmed biallelic proopiomelano-cortin (POMC) deficiency (including PCSK1) or biallelic leptin receptor (LEPR) deficiency caused by loss-of-function mutations [4]. The benefit assessment of setmelanotide is based on the 2 pivotal studies 012 and 015. Study 012 is an open-label, multicenter, single-arm, nonrandomized phase III study with a double-blind, placebo-controlled withdrawal phase to evaluate the efficacy and safety of setmelanotide in individuals with POMC-/PCKS1-deficiency obesity. Study 015 is an open-label, multi-center, single-arm, non-randomized Phase III study with a double-blind, placebo-controlled withdrawal phase to evaluate the efficacy and safety of setmelanotide in individuals with LEPR deficiency obesity. Because Studies 012 and 015 are studies without a control group, the potential for bias at the study and endpoint levels is considered high. Mortality: Based on studies 012 and 015, no conclusions can be drawn regarding the effects of setmelanotide on mortality in the present disease pattern. Morbidity: Basically, in the data of morbidity parameters, it should be noted that body weight is taken into account both in the evaluation of weight reduction and in the evaluation of BMI. Quality of life: For the endpoints of the endpoint category "quality of life" ("SF-36", "IWQOL-Lite", "PedsQL"), data are only available from less than 70% of the respective study populations (see quality of life). Therefore, the data are not presented in the benefit assessment. Safety: Overall, the interpretation of the safety results is difficult, as these are single-arm studies and the underlying comorbidities and sequelae required the use of concomitant treatments. As also stated in the EPAR (European Public Assessment Report), the comorbidities associated with the underlying disease and the chosen study design do not allow an adequate differentiation between the symptoms of the comorbidities and the drug-related side effects of setmelanotide. The occurrence of melanoma, prolonged penile erections, and depression/suicidal ideation are cited as important potential side effects. According to the EPAR, uncertainties regarding safety will be addressed through a planned registry (Post-Authorization Safety Study).

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/837/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5753/2022-12-01_AM-RL-XII_Setmelanotide_D-824_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/837/#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/