The MC4R pathway in the hypothalamus is a key neuronal pathway in regulating hunger, caloric intake, and energy expenditure1

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  • The BBSome
    plays a central role in cilia
    function, including trafficking of the leptin
    receptors (LEPR) to allow leptin activation and satiety signaling.
  • Leptin binding to LEPR triggers a signaling cascade, including secretion of alpha-melanocyte-stimulating hormone (α-MSH) from the POMC neuron, which binds to the MC4 receptor to regulate energy expenditure and satiety.
Functional MC4R pathway activity
Functional MC4R pathway activity

IMCIVREE is the first and only precision medicine to target impairment in the hypothalamic MC4R pathway, a root cause of hyperphagia and obesity in BBS1,6

  • IMCIVREE, an MC4R agonist, acts in place of alpha-melanocyte-stimulating hormone (α-MSH) to activate the MC4 receptor, to reestablish MC4R pathway activity.6-8
  • Activation of the MC4R pathway can help to increase satiety signals and energy expenditure, therefore reducing hunger, and consequently, food intake and weight.6
IMCIVREE activates the MC4 receptor in the MC4R pathway
IMCIVREE activates the MC4 receptor in the MC4R pathway
Learn more about the efficacy of IMCIVREE

MC4R=melanocortin-4 receptor; POMC=proopiomelanocortin.

References: 1. Eneli I et al. Appl Clin Genet. 2019;12:87-93. 2. Seo S et al. Hum Mol Genet. 2009;18(7):1323-1331. 3. Blaess S et al. J Clin Invest. 2021;131(8):e148903. doi:10.1172/JCI148903. 4. Huvenne H et al. Obes Facts. 2016;9(3):158-173. 5. Focșa IO et al. Biomed Rep. 2021;15(6):103. doi:10.3892/br.2021.1479. 6. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc. 7. Trapp CM et al. Curr Opin Endocrinol Diabetes Obes. 2023;30(2):136-140. 8. Haws R et al. Diabetes Obes Metab. 2020;22(11):2133-2140. doi:10.1111/dom.14133.

Important Safety Information

Indication

IMCIVREE is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to Bardet-Biedl syndrome (BBS).

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 BBS or other FDA-approved indications for IMCIVREE, including obesity associated with other genetic syndromes and general (polygenic) obesity

Contraindication

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 in males and sexual adverse reactions in females 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 Pigmentation and Darkening of Pre-existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmentary lesions.

Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: IMCIVREE is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs.

ADVERSE REACTIONS

  • Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, 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.

To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at 833-789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see the full Prescribing Information for additional Important Safety Information.

Important Safety Information

Indication

IMCIVREE is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to Bardet-Biedl syndrome (BBS).

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 BBS or other FDA-approved indications for IMCIVREE, including obesity associated with other genetic syndromes and general (polygenic) obesity

Contraindication

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 in males and sexual adverse reactions in females 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 Pigmentation and Darkening of Pre-existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmentary lesions.

Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: IMCIVREE is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs.

ADVERSE REACTIONS

  • Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, 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.

To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at 833-789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see the full Prescribing Information for additional Important Safety Information.