Genetic obesity caused by rare MC4R pathway diseases

Obesity is a multifactorial disease with a variety of phenotypes, clinical presentations, and treatment responses1,2

General obesity2

  • Can be due to:
    • Environmental factors
    • Multiple common genes interacting together (polygenic)
  • Can occur at any age, including later in life

Genetic obesity caused by
rare MC4R pathway 
 diseases2-4

  • Due to rare genetic variants/impairment of gene expression or function
  • Marked by hyperphagia and early-onset, severe obesity, both of which may develop as early as a few months old, but often appear in early childhood
  • These patients may benefit from targeted treatment for their specific disease

Monogenic obesity1
(POMC, PCSK1, LEPR deficiencies)

  • Rare and early-onset, severe obesity associated with endocrine disorders
  • Mainly due to variants in the MC4R pathway involved in food intake regulation

Syndromic obesity (BBS)5-7

  • Severe obesity associated with additional phenotypes (ie, dysmorphic features, organ-specific developmental abnormalities)

Per the 2023 AAP and 2023 OMA guidelines, it is important to treat obesity promptly, using the most intensive, comprehensive treatment available, including pharmacotherapy when indicated3,8

 
Learn more about hyperphagia in BBS

AAP=American Academy of Pediatrics; LEPR=leptin receptor; MC4R=melanocortin-4 receptor; OMA=Obesity Medicine Association; PCSK1=proprotein convertase subtilisin/kexin type 1; POMC=proopiomelanocortin.

References: 1. Loos RJF et al. Nat Rev Genet. 2022;23(2):120-133. doi:10.1038/s41576-021-00414-z. 2. Huvenne H et al. Obes Facts. 2016;9(3):158-173. 3. Hampl SE et al. Pediatrics. 2023;151(2):e202206064. doi:10.1542/peds.2022-060640. 4. Eneli I et al. Appl Clin Genet. 2019;12:87-93. 5. Manara E et al. Ital J Pediatr. 2019;45(1):72. 6. Forsythe E et al. Front Pediatr. 2018;6:23. doi:10.3389/fped.2018.00023. 7. Vaisse C et al. Cold Spring Harb Perspect Biol. 2017;9(7):a028217. 8. Tondt J et al. Obesity Algorithm® 2023. Obesity Medicine Association; 2023. Accessed August 11, 2023. https://obesitymedicine.org/obesity-algorithm.

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

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.

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

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.

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.