A systematic literature review of economic evaluations of setmelanotide

Purpose: This systematic literature review (SLR) aimed to assess the economic value of setmelanotide, a selective melanocortin-4 receptor agonist, in the treatment of rare genetic diseases of obesity (RGDOs), specifically Bardet-Biedl syndrome (BBS), pro-opiomelanocortin (POMC) deficiency, and leptin receptor (LEPR) deficiency. Methods: The SLR was conducted according to PRISMA guidelines and registered on PROSPERO. Systematic searches were performed in Embase, MEDLINE/PubMed, and Global Health, supplemented by manual searches and reference screening. Inclusion criteria included full economic evaluations (cost-effectiveness and cost-utility analyses) published in English since 2019. Data extraction and quality assessment followed established checklists (BMJ, CHEERS 2022), with findings synthesised descriptively due to heterogeneity in study designs and settings. Results: Four studies (one CEA, three CUAs) met inclusion criteria, all employing model-based frameworks from a healthcare payer perspective with a lifetime horizon. Incremental cost-effectiveness ratios (ICERs) varied: NICE appraisals in the UK suggested potentially favorable or even negative ICERs, while the Canadian CADTH review reported ICERs exceeding CAD $2 million/QALY, far above conventional willingness-to-pay thresholds. Key drivers included drug acquisition cost, severity of hyperphagia, and caregiver burden. All studies noted significant uncertainty due to limited long-term data and small patient populations. Conclusions: While setmelanotide demonstrates clinical benefit in RGDOs, its high cost poses substantial challenges to conventional pharmacoeconomic evaluations. Adoption may require significant price reductions or alternative value assessment frameworks, particularly for rare diseases. Further research is needed to address long-term effectiveness and ethical considerations in economic evaluations.