Imcivree (setmelanotide) for acquired hypothalamic obesity
Fact-checked by What is Imcivree for acquired hypothalamic obesity?
Imcivree (setmelanotide) is an approved treatment used to help support and maintain weight loss in people with acquired hypothalamic obesity (aHO) who are at least 4 years old.
In aHO, damage to a brain region called the hypothalamus disrupts hormonal signals that control appetite and energy use, including those from the melanocortin 4 receptor (MC4R) signaling pathway. People with aHO often experience excessive feelings of hunger and use less energy while at rest, resulting in rapid and sustained weight gain.
Imcivree is designed to restore activity in the MC4R pathway, thereby helping to increase energy expenditure and boost brain signals that communicate a feeling of fullness after eating. Combined, these effects are expected to reduce hunger, ultimately resulting in weight loss and maintenance of that reduction in people with aHO.
Rhythm Pharmaceuticals markets Imcivree for aHO and certain other rare types of obesity, including Bardet-Biedl syndrome. It is given as a once-daily subcutaneous (under-the-skin) injection.
Therapy snapshot
| Brand name | Imcivree |
| Chemical name | Setmelanotide |
| Usage | Used for weight loss and maintenance in aHO |
| Administration | Subcutaneous injection |
Who with aHO can take Imcivree?
In the U.S., Imcivree is approved to reduce excess body weight and maintain the reduction long-term in people with aHO who are at least 4 years old. It is also approved in Europe for a similar indication.
The medication is contraindicated, or should not be used by, people with a history of serious immune reactions (hypersensitivity) to Imcivree or any of its ingredients.
It also isn’t recommended for people who are breastfeeding.
How is Imcivree administered in aHO?
Imcivree is administered as a subcutaneous injection, once at the beginning of each day.
Patients or caregivers can administer Imcivree at home after training from a healthcare professional. Vials of Imcivree should be refrigerated when not in use. The injection site should be rotated daily between the abdomen, thigh, and arm.
The recommended starting dose of Imcivree for people with aHO is 0.5 mg per day. If the medication is well tolerated after 2 weeks, the dose may be gradually increased. The recommended maintenance dose for people ages 6 and older is 3 mg daily; for younger children, it is calculated based on body weight.
The dosage may need to be adjusted for people with kidney problems.
Imcivree in aHO clinical trials
Imcivree’s approval for aHO was largely supported by data from the Phase 3 TRANSCEND clinical trial (NCT05774756), which tested daily Imcivree versus a placebo in 142 people with aHO, ages 4 and older. The results showed that after a year of treatment:
- mean body mass index (BMI) — a ratio of weight and height that can approximate body fat — dropped by 15.8% with Imcivree and increased by 2.6% with the placebo, amounting to a significant, 18.4% relative difference
- about three-quarters of Imcivree-treated participants experienced at least a 5% reduction in BMI, compared with about 10% of the placebo group
- Imcivree was associated with significant reductions in hunger compared with the placebo
An earlier Phase 2 study (NCT04725240) showed that 16 of 18 participants with aHO completed the study, and all experienced at least a 5% reduction in BMI after four months of treatment. Across all participants, the mean BMI reduction was 15%.
Imcivree side effects
The most common side effects of Imcivree across all approved indications include:
- darkening of the skin
- injection site reactions
- nausea
- headache
- diarrhea
- stomach pain
- vomiting
- depression
- spontaneous penile erections
Imcivree also comes with warnings and precautions for side effects that require careful monitoring, including:
- disturbances in sexual arousal
- serious depression or thoughts of suicide
- serious hypersensitivity reactions, including a life-threatening reaction called anaphylaxis
- new skin moles or darkening of existing moles
- acute adrenal insufficiency, a severe lack of the hormone cortisol that can be life-threatening, in people with an existing cortisol deficiency
- sodium imbalances in people with central diabetes insipidus, a type of diabetes that originates in the brain
Patients who experience signs of a hypersensitivity reaction or erections lasting longer than four hours should seek emergency medical care. Imcivree may need to be discontinued if suicidal thoughts or behaviors or persistent and clinically significant depression occur.
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