POMC, PCSK1, and LEPR deficiency are all rare autosomal recessive disorders that lead to hyperphagia and early-onset, severe obesity1,2

POMC
deficiency

Proopiomelanocortin deficiency

PCSK1
deficiency

Proprotein convertase subtilisin/kexin type 1 deficiency

LEPR
deficiency

Leptin receptor deficiency

POMC, PCSK1, and LEPR deficiency impact various systems throughout the body1,3-9

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Brain

  • Hyperphagia and consequent obesity
Endocrine icon

Endocrine

  • Adrenal insufficiency

Additional clinical features of POMC may include:

  • Endocrine: Hypothyroidism, adolescent-onset growth hormone deficiency, hypoglycemia
  • Reproductive: Hypogonadotropic hypogonadism
  • Physical: Red hair and light skin pigmentation
  • Hepatic: Liver failure

These conditions can be difficult to diagnose based solely on clinical manifestations, but genetic testing may be able to help. For more information about genetic testing for POMC, PCSK1, and LEPR deficiency, please visit UncoveringRareObesity.com

 

Uncovering Rare Obesity® can help support a diagnosis of POMC, PCSK1, or LEPR deficiency

A no-charge,* extensive genetic testing program for MC4R pathway diseases

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Extensive panel offers broad insights

The gene panel includes 79 genes and 1 chromosome region, reflective of nearly all of the most frequently tested genes associated with obesity.

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Tailored support for results interpretation

Access to a geneticist to help interpret results and licensed genetic counselors for your patients are available. Services are provided through third-party partners.

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Testing conducted by a laboratory partner

DNA testing is conducted by PreventionGenetics, a CLIA-accredited clinical laboratory.

Swab kit icon

Blood and OCD-100 buccal swab
sample collection kits are available.

 

For more information about the genetic testing program, visit Uncovering Rare Obesity.com

*Rhythm Pharmaceuticals covers the cost of the test and provides sample collection kits. Patients are responsible for office visit, sample collection, or other costs.

Discover the different types of obesity

CLIA=Clinical Laboratory Improvement Amendments; GI=gastrointestinal; LEPR=leptin receptor; MC4R=melanocortin-4 receptor; PCSK1=proprotein convertase subtilisin/kexin type 1; POMC=proopiomelanocortin.

References: 1. Styne DM et al. J Clin Endocrinol Metab. 2017;102(3):709-757. 2. Malhotra S et al. J Pediatr Genet. 2021;10(3):194-204. doi:10.1055/s-0041-1731035. 3. Coll AP et al. J Clin Endocrinol Metab. 2004;89(6):2557-2562. doi:10.1210/jc.2004-0428. 4. Bereket A et al. Obes Rev. 2012;13(9):780-798. doi:10.1111/j.1467-789X.2012.01004.x. 5. Gregoric N et al. Front Endocrinol (Lausanne). 2021;12:689387.bdoi:10.3389/fendo.2021.689387. 6. Stijnen P et al. Endocr Rev. 2016;37(4):347-371. doi:10.1210/er.2015-1117. 7. Farooqi IS et al. N Engl J Med. 2007;356(3):237-247. doi:10.1056/NEJMoa063988. 8. Farooqi IS et al. J Endocrinol. 2014;223(1):T63-T70. doi:10.1530/JOE-14-0480. 9. Elias CF et al. Cell Mol Life Sci. 2013;70(5):841-862. doi:10.1007/s00018-012-1095-1.

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 pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test 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

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 pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test 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

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.