FDA approved for patients 2 years and older with obesity due to POMC, PCSK1, or LEPR deficiency

Help switch on the POWER of the PATHWAY^™

Actor portrayals

IMCIVREE is the first and only treatment that targets impairment of the hypothalamic MC4R pathway, a root cause of hyperphagia and obesity due to POMC, PCSK1, and LEPR deficiencies.^1-3

Actor portrayals

Doctor activating the power of the hypothalamic MC4R pathway

Doctor activating the power of the hypothalamic MC4R pathway

IMCIVREE targets a root cause of hyperphagia and obesity in POMC, PCSK1, and LEPR deficiencies^1,2

Impaired MC4R pathway function²

In people with POMC, PCSK1, or LEPR deficiency, genetic variants can cause disrupted signaling.

α-MSH production is impaired or deficient, preventing activation of the MC4 receptor and impairing regulation of energy expenditure and satiety signaling.

MC4R pathway impairment showing disrupted signaling affecting satiety and energy regulation — Impaired MC4R pathway function: In people with POMC, PCSK1, or LEPR deficiency, genetic variants can cause disrupted signaling. α-MSH production is impaired or deficient, preventing activation of the MC4 receptor and impairing regulation of energy expenditure and satiety signaling.

Reestablished MC4R pathway function¹

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

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

MC4R pathway activation showing IMCIVREE restoring signaling to increase satiety and energy expenditure — Reestablished MC4R pathway function: IMCIVREE is an MC4 receptor agonist that acts in place of α-MSH to help activate the MC4R pathway. This activation helps to increase satiety and energy expenditure, therefore reducing hunger, food intake, and weight.

IMCIVREE helps reestablish and maintain MC4R pathway function, providing the foundation for effective long-term treatment of obesity due to POMC, PCSK1, or LEPR deficiency.^1,4

About POMC, PCSK1, and LEPR deficiencies

Rare autosomal recessive disorders²

Lead to hyperphagia and early-onset, severe obesity, mainly due to genetic variants in the MCR4 pathway²

Can be difficult to diagnose based solely on clinical manifestations, so genetic testing is required to confirm a diagnosis^1,5

Learn if IMCIVREE may be appropriate for your patients with POMC, PCSK1, or LEPR deficiency.

Connect with a Rep

See efficacy data for IMCIVREE in two age groups.

See Efficacy for Ages 2 to <6 See Efficacy for Ages 6+

α-MSH=alpha-melanocyte stimulating hormone, LEPR=leptin receptor, MC4R=melanocortin-4 receptor, PCSK1=proprotein convertase subtilisin/kexin type 1, POMC=proopiomelanocortin.

Indication

IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

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:

Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign
Other types of obesity not related to POMC, PCSK1, or LEPR deficiency, 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.

Adverse Reactions

Most common adverse reactions (incidence ≥20%) included injection site reactions, skin hyperpigmentation, nausea, headache, diarrhea, abdominal pain, back pain, fatigue, vomiting, depression, upper respiratory tract infection, and spontaneous penile erection

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. Eneli I, Xu J, Webster M, et al. Tracing the effect of the melanocortin-4 receptor pathway in obesity: study design and methodology of the TEMPO registry. Appl Clin Genet. 2019;12:87-93. Published 2019 Jun 5. doi:10.2147/TACG.S199092 3. Approved Drug Products with Therapeutic Equivalence Evaluations. 45th ed. Food and Drug Administration; 2025:1756. 4. Haqq AM, Chung WK, Dollfus H, et al. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period. Lancet Diabetes Endocrinol. 2022;10(12):859-868. doi:10.1016/S2213-8587(22)00277-7 5. Malhotra S, Sivasubramanian R, Srivastava G. Evaluation and management of early onset genetic obesity in childhood. J Pediatr Genet. 2021;10(3):194-204. doi:10.1055/s-0041-1731035

Indication

IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

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:

Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign
Other types of obesity not related to POMC, PCSK1, or LEPR deficiency, 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.

Adverse Reactions

Most common adverse reactions (incidence ≥20%) included injection site reactions, skin hyperpigmentation, nausea, headache, diarrhea, abdominal pain, back pain, fatigue, vomiting, depression, upper respiratory tract infection, and spontaneous penile erection

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. Eneli I, Xu J, Webster M, et al. Tracing the effect of the melanocortin-4 receptor pathway in obesity: study design and methodology of the TEMPO registry. Appl Clin Genet. 2019;12:87-93. Published 2019 Jun 5. doi:10.2147/TACG.S1990923. Approved Drug Products with Therapeutic Equivalence Evaluations. 45th ed. Food and Drug Administration; 2025:1756.4. Haqq AM, Chung WK, Dollfus H, et al. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period. Lancet Diabetes Endocrinol. 2022;10(12):859-868. doi:10.1016/S2213-8587(22)00277-75. Malhotra S, Sivasubramanian R, Srivastava G. Evaluation and management of early onset genetic obesity in childhood. J Pediatr Genet. 2021;10(3):194-204. doi:10.1055/s-0041-1731035