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FDA approved for patients 4 years and older with acquired hypothalamic obesity (HO)

Help switch on the POWER of the PATHWAY™

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IMCIVREE is the first and only treatment that targets impairment of the hypothalamic MC4R pathway, the root cause of weight gain and increased hunger in acquired HO.1,2

Doctor on lift in front of large brain, activating MC4R pathway switch

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Acquired HO is a distinct disease of MC4R pathway impairment2

The hypothalamic MC4R pathway plays a fundamental role in regulating energy intake and expenditure2

  • Injury to the hypothalamic-pituitary region can impair production of various hormones, including α-melanocyte stimulating hormone (α-MSH)—the endogenous MC4 receptor ligand—leading to MC4R pathway impairment and acquired HO1,2
  • Patients with acquired HO experience a high burden of comorbidities and decreased quality of life3

Reestablishing MC4R pathway function is foundational for effective long-term management of acquired HO.1,2,4

Looking for information about the causes and symptoms of acquired HO? Find out more about acquired HO.

IMCIVREE targets the root cause of acquired HO1

Impaired MC4R pathway function in acquired HO

Deficient α-MSH production due to hypothalamic injury leads to decreased MC4 receptor activation across the central nervous system.1,2

Impaired MC4R pathway function can dysregulate energy balance and satiety, which may lead to increased hunger, food intake, and weight that require targeted MC4R pathway intervention.1,2

MC4R pathway diagram showing POMC neuron signaling regulating hunger, energy expenditure, and body weight

Reestablished MC4R pathway function

IMCIVREE is an MC4 receptor agonist that acts in place of α-MSH to help activate the MC4R pathway.1

MC4R pathway activation helps increase energy expenditure and satiety, reducing hunger, food intake, and weight.1,4

Restored MC4R pathway diagram showing IMCIVREE activating MC4R signaling to regulate hunger and energy expenditure

IMCIVREE helps reestablish and maintain MC4R pathway function, providing the foundation for effective long-term treatment of acquired HO.1,2

Learn if IMCIVREE may be appropriate for your patients with acquired HO.

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IMCIVREE has been shown to deliver significant reductions in BMI and hunger.1

See Efficacy for Ages 4 to <18See Efficacy for Ages 18+

α-MSH=alpha-melanocyte stimulating hormone, BMI=body mass index, HO=hypothalamic obesity, MC4=melanocortin-4, MC4R=melanocortin-4 receptor.

Indication

IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 4 years and older with acquired hypothalamic obesity (HO).

Limitations of Use

IMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective:

  • Other types of obesity not related to acquired hypothalamic obesity or other FDA-approved indications for IMCIVREE, including obesity associated with other genetic syndromes and general (polygenic) obesity

Important Safety Information

Contraindications

Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported.

Warnings and Precautions

Disturbance in Sexual Arousal: Spontaneous penile erections and increased frequency of penile erections in males have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.

Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur.

Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE.

Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Generalized or focal increases in skin pigmentation occurred in the majority of IMCIVREE-treated patients. IMCIVREE may also cause development of new melanocytic nevi or darkening of pre-existing nevi. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented lesions.

Acute Adrenal Insufficiency with Acquired HO: Patients with acquired HO and secondary adrenal insufficiency reported serious adverse reactions related to acute adrenal insufficiency in 5% of IMCIVREE-treated patients and no placebo-treated patients. In patients with secondary adrenal insufficiency, monitor for clinical signs of acute adrenal insufficiency.

Sodium Imbalance in Patients with Acquired HO and Central Diabetes Insipidus: Patients with acquired HO and concomitant central diabetes insipidus (DI)/arginine vasopressin (AVP) deficiency reported hyponatremia in 6% of IMCIVREE-treated patients and 2% of placebo-treated patients and hypernatremia in 5% of IMCIVREE-treated patients and 4% of placebo-treated patients. Monitor serum sodium levels with changes in fluid intake and hydration status. Adjust the doses of concomitant therapies for DI/AVP deficiency as needed.

Adverse Reactions

  • Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, nausea, vomiting, and headache

Use in Specific Populations

Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Please see full Prescribing Information for additional Important Safety Information.

References: 1. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc., 2026. 2. Roth CL, Scimia C, Shoemaker AH, et al. Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial. Lancet Diabetes Endocrinol. 2024;12(6):380-389. doi:10.1016/S2213-8587(24)00087-1 3. Müller HL, Witte J, Surmann B, et al. Treatment of patients with tumor/treatment-related hypothalamic obesity in the first two years following surgical treatment or radiotherapy. Sci Rep. 2025;15(1):2118. Published 2025 Jan 16. doi:10.1038/s41598-025-85262-1 4. Data on file. Rhythm Pharmaceuticals, Inc. Boston, MA.

Indication and Important Safety Information

Indication

IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 4 years and older with acquired hypothalamic obesity (HO).

Limitations of Use

IMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective:

  • Other types of obesity not related to acquired hypothalamic obesity or other FDA-approved indications for IMCIVREE, including obesity associated with other genetic syndromes and general (polygenic) obesity

Important Safety Information

Contraindications

Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported.

Warnings and Precautions

Disturbance in Sexual Arousal: Spontaneous penile erections and increased frequency of penile erections in males have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.

Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur.

Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE.

Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Generalized or focal increases in skin pigmentation occurred in the majority of IMCIVREE-treated patients. IMCIVREE may also cause development of new melanocytic nevi or darkening of pre-existing nevi. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented lesions.

Acute Adrenal Insufficiency with Acquired HO: Patients with acquired HO and secondary adrenal insufficiency reported serious adverse reactions related to acute adrenal insufficiency in 5% of IMCIVREE-treated patients and no placebo-treated patients. In patients with secondary adrenal insufficiency, monitor for clinical signs of acute adrenal insufficiency.

Sodium Imbalance in Patients with Acquired HO and Central Diabetes Insipidus: Patients with acquired HO and concomitant central diabetes insipidus (DI)/arginine vasopressin (AVP) deficiency reported hyponatremia in 6% of IMCIVREE-treated patients and 2% of placebo-treated patients and hypernatremia in 5% of IMCIVREE-treated patients and 4% of placebo-treated patients. Monitor serum sodium levels with changes in fluid intake and hydration status. Adjust the doses of concomitant therapies for DI/AVP deficiency as needed.

Adverse Reactions

  • Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, nausea, vomiting, and headache

Use in Specific Populations

Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Please see full Prescribing Information for additional Important Safety Information.

References:1. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc., 2026.2. Roth CL, Scimia C, Shoemaker AH, et al. Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial. Lancet Diabetes Endocrinol. 2024;12(6):380-389. doi:10.1016/S2213-8587(24)00087-13. Müller HL, Witte J, Surmann B, et al. Treatment of patients with tumor/treatment-related hypothalamic obesity in the first two years following surgical treatment or radiotherapy. Sci Rep. 2025;15(1):2118. Published 2025 Jan 16. doi:10.1038/s41598-025-85262-14. Data on file. Rhythm Pharmaceuticals, Inc. Boston, MA.
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