Setmelanotide
Setmelanotide is a daily injection that switches back on the brain's fullness signal. Approved for rare genetic causes of obesity, it is being tested for the relentless weight gain that follows damage to the hypothalamus from craniopharyngioma surgery or radiotherapy.
Overview
Setmelanotide is Rhythm Pharmaceuticals' melanocortin-4 receptor agonist. The FDA approved it in 2020 for chronic weight management in obesity due to POMC, PCSK1 or LEPR deficiency, and later for Bardet-Biedl syndrome. It is injected under the skin once daily and reduces hunger and weight in patients whose hypothalamic satiety pathway is broken upstream of the receptor.
Hypothalamic obesity after craniopharyngioma is an acquired lesion of the same pathway and resists diet and conventional drugs. A phase 2 trial showed weight loss in patients with acquired hypothalamic obesity, and a phase 3 trial followed. The craniopharyngioma page names it, with GLP-1 agonists and oxytocin, among the treatments under study for hypothalamic obesity.
Activates the melanocortin-4 receptor downstream of the leptin-POMC pathway in the hypothalamus, restoring the satiety signal that is lost when the hypothalamus is damaged by a craniopharyngioma or its treatment.
1.Setmelanotide slips into a pocket on its target.
- AmivantamabApproved
- CamizestrantApproved
- Comprehensive genomic profilingStandard of care
- Liquid biopsy (ctDNA)Standard of care
- LorlatinibApproved
- MRD / molecular residual disease testingEstablished
- ADC payload neutralisersPhase 1
- BGB-16673Phase 3
- Bispecific ADCPhase 3
- BRUIN CLL-321Positive
- CaDAnCe-304Recruiting
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
- A clone report from blood at every treatment cycle
- A fast route to the matched drug when it is licensed for another cancer
- A multi-cancer platform trial of adaptive (dose-holiday) therapy
- A national rapid research autopsy network for end-stage cancer
- A standard evolvability score for every tumour
- A standing platform trial that assigns treatment by how the tumour escaped
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance atlas · Lines of therapy.
Approvals
| Region | Year | Indication |
|---|---|---|
| US | 2020 | Chronic weight management in obesity due to POMC, PCSK1 or LEPR deficiency |
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Latest papers
topQuery for this drug: (TITLE:"Setmelanotide" OR ABSTRACT:"Setmelanotide" OR TITLE:"Imcivree" OR ABSTRACT:"Imcivree" OR TITLE:"RM-493" OR ABSTRACT:"RM-493") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Setmelanotide, not a curated reading list.