Imcivree (setmelanotide) for Bardet-Biedl syndrome
Fact-checked by What is Imcivree for Bardet-Biedl syndrome?
Imcivree (setmelanotide) is an approved daily injection therapy used to help children and adults with Bardet-Biedl syndrome (BBS) manage their weight.
BBS is a genetic condition that affects specialized cell structures called cilia, which play several important roles throughout the body, including in the brain region called the hypothalamus. Researchers believe that BBS-related cilia dysfunction in the hypothalamus impairs the melanocortin 4 receptor (MC4R) signaling pathway, which helps regulate hunger. As a result, many people with BBS experience excessive hunger, or hyperphagia, and obesity.
Imcivree aims to restore MC4R signaling, helping the body sense fullness after eating. This may reduce hyperphagia in some people with BBS and support weight loss and its long-term maintenance.
Rhythm Pharmaceuticals markets Imcivree, which is administered as a daily subcutaneous (under-the-skin) injection. In the U.S., the medication is also approved for other rare forms of obesity, including acquired hypothalamic obesity and genetic conditions that affect MC4R signaling. The company is now testing Imcivree as a treatment for Prader-Willi syndrome, a genetic disorder that can cause hyperphagia.
Therapy snapshot
| Brand name | Imcivree |
| Chemical name | Setmelanotide |
| Usage | Used to reduce excess body weight and maintain weight loss in BBS |
| Administration | Subcutaneous injection |
Who with Bardet-Biedl syndrome can take Imcivree?
In the U.S., Imcivree is approved to reduce excess body weight and maintain long-term weight reduction in adults and children ages 2 and older with BBS. It is also approved elsewhere, including in the European Union and Canada, though specific indications may vary.
Imcivree is contraindicated, or should not be used, by people who have previously experienced serious immune reactions (hypersensitivity) to Imcivree or any of its ingredients.
How is Imcivree administered in BBS?
Imcivree is administered as a subcutaneous injection once at the beginning of each day, with injection sites rotating between the abdomen, thigh, and arm.
After training from a healthcare professional, people with BBS or their caregivers can give the injections at home. Imcivree comes in vials, which should be stored in a refrigerator.
The recommended dose is determined by age:
- ages 12 and older: 2 mg for the first two weeks, followed by a 3 mg maintenance dose
- ages 6-11: 1 mg for the first two weeks, gradually increased to a 3 mg maintenance dose
- ages 2-5: 0.5 mg for the first two weeks, followed by weight-based maintenance dosing
At any point, doses may need to be reduced if intolerable side effects occur. Dose adjustments may also be required for people with kidney impairments, which can be a symptom of BBS.
Imcivree in Bardet-Biedl syndrome clinical trials
Imcivree’s approval for BBS was primarily supported by two Phase 3 clinical trials:
- A Phase 3 study (NCT03746522) involved people with BBS-related obesity, ages 6 and older. Results showed that about a third of participants experienced a 10% or greater weight reduction after a year of treatment. Imcivree was associated with greater reductions in body mass index (BMI) — a ratio of height and weight often used to estimate body fat — than a placebo after about 3.5 months. Most participants experienced improvements in quality of life while taking Imcivree, and many reported reduced hunger.
- The Phase 3 VENTURE trial (NCT04966741) involved children ages 2 to 5, including five with BBS-related obesity, all of whom received daily Imcivree for a year. The results showed that four out of five BBS patients achieved a clinically meaningful reduction in BMI for their age, height, and gender. Of the three participants who were treated for 1.5 years, all had clinically meaningful weight reductions.
Imcivree side effects
The most common side effects of Imcivree across all of its approved indications include:
- darkening of the skin
- injection site reactions
- nausea
- headache
- diarrhea
- abdominal pain
- vomiting
- depression
- spontaneous penile erections
Imcivree also comes with warnings and precautions for:
- disturbances in sexual arousal
- serious depression or thoughts of suicide
- serious hypersensitivity reactions, including anaphylaxis, a life-threatening reaction
- new skin moles or darkening of existing moles
Patients who experience erections lasting longer than 4 hours or any signs of a hypersensitivity reaction should seek emergency medical care.
Those using Imcivree will be monitored for signs of worsening mental health; the medication may need to be stopped if suicidal thoughts or behaviors emerge or if depression becomes clinically significant or persistent.
While skin changes associated with Imcivree aren’t usually dangerous, doctors will regularly monitor them.
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