WHA

Imcivree (setmelanotide) – PA, NF

Indications for Prior Authorization

Imcivree (setmelanotide)
  • For diagnosis of Obesity
    Indicated to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients 2 years of age and older with monogenic or syndromic obesity due to:

    1) 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)

    2) Bardet-Biedl Syndrome (BBS)

  • For diagnosis of 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 BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity

Criteria

Imcivree

Prior Authorization (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Obesity due to POMC, PCSK1, LEPR deficiency

  • Patient has been diagnosed with obesity defined by one of the following:
    • Both of the following:
      • Patient is 6 years of age or older
        • AND
      • One of the following:
        • BMI greater than or equal to 30 kg/m2 for adults 18 years of age or older
        • Weight greater than or equal to 95th percentile using growth chart assessments for pediatric patients
      OR
    • Both of the following:
      • Patient is 2 years of age to less than 6 years of age
        • AND
      • Both of the following: [6-7]
        • Patient weighs at least 15 kg
        • Weight greater than or equal to 97th percentile using growth chart assessments for pediatric patients
    AND
  • Obesity is due to one of the following genetic deficiencies:
    • Proopiomelanocortin (POMC)
    • Proprotein convertase subtilisin/kexin type 1 (PCSK1)
    • Leptin receptor (LEPR)
    AND
  • Other causes or types of obesity have been ruled out (e.g., obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign; obesity associated with other genetic syndromes; polygenic obesity)
    • AND
  • Baseline Z-score [C, 6]
Imcivree

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Obesity due to POMC, PCSK1, LEPR deficiency

  • For patients 6 years of age or older, one of the following:
    • Both of the following: [A]
      • Patient has been on therapy for less than 12 months
      • Weight loss of greater than or equal to 5% of baseline body weight
      OR
    • Both of the following:
      • Patient has been on therapy for 12 months or more
      • Weight loss of greater than or equal to 10% of baseline body weight
      OR
    • Both of the following: [5]
      • Patient has been on therapy for 12 months or more
      • Z-score of 0 to negative 1 vs baseline
    OR
  • For patient 2 years of age to less than 6 years of age, a decrease in the BMI z score of 0.2 points or greater [C, 6]
Imcivree

Non Formulary (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Obesity due to POMC, PCSK1, LEPR deficiency

  • Submission of medical records (e.g., chart notes) confirming diagnosis of obesity as defined by one of the following:
    • Both of the following:
      • Patient is 6 years of age or older
        • AND
      • One of the following:
        • BMI greater than or equal to 30 kg/m2 for adults 18 years of age or older
        • Weight greater than or equal to 95th percentile using growth chart assessments for pediatric patients
      OR
    • Both of the following:
      • Patient is 2 years of age to less than 6 years of age
        • AND
      • Both of the following: [6-7]
        • Patient weighs at least 15 kg
        • Weight greater than or equal to 97th percentile using growth chart assessments for pediatric patients
    AND
  • Submission of medical records (e.g., chart notes) confirming obesity is due to one of the following genetic deficiencies:
    • Proopiomelanocortin (POMC)
    • Proprotein convertase subtilisin/kexin type 1 (PCSK1)
    • Leptin receptor (LEPR)
    AND
  • Submission of medical records (e.g., chart notes) confirming other causes or types of obesity have been ruled out (e.g., obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign; obesity associated with other genetic syndromes; polygenic obesity)
    • AND
  • Submission of medical records (e.g., chart notes) confirming baseline Z-score [5]
Imcivree

Non Formulary (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Obesity due to POMC, PCSK1, LEPR deficiency

  • For patients age 6 years of age or older, submission of medical records (e.g., chart notes) confirming one of the following:
    • Both of the following: [A]
      • Patient has been on therapy for less than 12 months
      • Weight loss of greater than or equal to 5% of baseline body weight
      OR
    • Both of the following:
      • Patient has been on therapy for 12 months or more
      • Weight loss of greater than or equal to 10% of baseline body weight
      OR
    • Both of the following: [5]
      • Patient has been on therapy for 12 months or more
      • Z-score of 0 to negative 1 vs baseline
    OR
  • For patient 2 years of age to less than 6 years of age, submission of medical records (e.g., chart notes) confirming a decrease in the BMI z score of 0.2 points or greater
Imcivree

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Obesity Due to Bardet-Biedl syndrome (BBS)

  • Diagnosis of Bardet-Biedl syndrome (BBS)
    • AND
  • Patient has been diagnosed with obesity defined by one of the following:
    • Both of the following:
      • Patient is 6 years of age or older
        • AND
      • One of the following:
        • BMI greater than or equal to 30 kg/m2 for adults 18 years of age or older
        • Weight greater than or equal to 95th percentile using growth chart assessments for pediatric patients
      OR
    • Both of the following: [6-7]
      • Patient is 2 years of age to less than 6 years of age
        • AND
      • Both of the following:
        • Patient weighs at least 15 kg
        • Weight greater than or equal to 97th percentile using growth chart assessments for pediatric patients
    AND
  • Other causes or types of obesity have been ruled out (e.g., obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign; obesity associated with other genetic syndromes; polygenic obesity)
    • AND
  • Baseline Z-score [C, 6]
Imcivree

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Obesity Due to Bardet-Biedl syndrome (BBS)

  • For patients 6 years of age or older, one of the following: [B]
    • Both of the following: [A]
      • Patient has been on therapy for less than 12 months
      • Weight loss of greater than or equal to 5% of baseline body weight
      OR
    • Both of the following: [5]
      • Patient has been on therapy for 12 months or more
      • Z-score of 0 to negative 1 vs baseline
    OR
  • For patients 2 years of age to less than 6 years of age, a decrease in the BMI z score of 0.2 points or greater [C, 6]
Imcivree

Non Formulary (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Obesity Due to Bardet-Biedl syndrome (BBS)

  • Diagnosis of Bardet-Biedl syndrome (BBS)
    • AND
  • Submission of medical records (e.g., chart notes) confirming diagnosis of obesity as defined by one of the following:
    • Both of the following:
      • Patient is 6 years of age or older
        • AND
      • One of the following:
        • BMI greater than or equal to 30 kg/m2 for adults 18 years of age or older
        • Weight greater than or equal to 95th percentile using growth chart assessments for pediatric patients
      OR
    • Both of the following: [6-7]
      • Patient is 2 years of age to less than 6 years of age
        • AND
      • Both of the following:
        • Patient weighs at least 15 kg
        • Weight greater than or equal to 97th percentile using growth chart assessments for pediatric patients
    AND
  • Submission of medical records (e.g., chart notes) confirming other causes or types of obesity have been ruled out (e.g., obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign; obesity associated with other genetic syndromes; polygenic obesity)
    • AND
  • Submission of medical records (e.g., chart notes) confirming baseline z -score
Imcivree

Non Formulary (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Obesity Due to Bardet-Biedl syndrome (BBS)

  • For patent age 6 years of age or older, submission of medical records (e.g., chart notes) confirming one of the following: [B]
    • Both of the following: [A]
      • Patient has been on therapy for less than 12 months
      • Weight loss of greater than or equal to 5% of baseline body weight
      OR
    • Both of the following: [5]
      • Patient has been on therapy for 12 months or more
      • Z-score of 0 to negative 1 vs baseline
    OR
  • For patient 2 years of age to less than 6 years of age, submission of medical records (e.g., chart notes) confirming a decrease in the BMI z score of 0.2 points or greater

  • Guideline ID
    GL-164720

  • Formulary
    premium

  • Effective date
    Apr 1, 2025

  • P&T approval date

P & T Revisions

2025-02-05, 2024-03-05, 2023-02-27, 2022-08-11, 2022-06-09, 2022-01-10, 2021-03-30, 2021-02-09

  1. Imcivree Prescribing Information. Rhythm Pharmaceuticals, Inc. Boston, MA. December 2024.
  2. Micromedex Healthcare Series [database on the Internet]. Greenwood Village (CO): IBM Corporation.; Updated periodically. Available by subscription at: https://www.micromedexsolutions.com/. Accessed January 8, 2021.
  3. Perreault, M. Genetic contribution and pathophysiology of obesity. UpToDate. www.uptodate.com. Updated November 22, 2019. Accessed January 8, 2021.
  4. Barlow SE and the Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 2007;120 Supplement December 2007:S164—S192.
  5. Clinical Consult January 30, 2025.
  6. ClinicalTrails.gov. Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity. Available at: https://clinicaltrials.gov/study/NCT04966741?cond=NCT04966741&rank=1#participation-criteria. Accessed January 21, 2025.
  7. Argente, J., Verge, C., Okorie, U., et al. Setmelanotide in patients aged 2–5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial. Available at: file:///C:/Users/kdekhtaw/AppData/Local/Microsoft/Windows/INetCache/Content.Outlook/3J33L6NQ/Argente%20et%20al%202025.pdf. Accessed January 21, 2025.
  1. For obesity due to POMC, PCSK1, or LEPR deficiency, patient should be evaluated for response to Imcivree after 12-16 weeks of treatment. If a patient has not lost at least 5% of baseline body weight or 5% of baseline BMI, it is recommended to discontinue Imcivree as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment. [1]
  2. For obesity due to BBS, patient should be evaluated for response to Imcivree after one year of treatment. If a patient has not lost at least 5% of baseline body weight or 5% of baseline BMI for patients aged less than 18 years, discontinue Imcivree as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment. [1]
  3. The co-primary endpoints at week 52 were the percentage of patients reaching a 0·2-point decrease or greater in BMI Z score (a statistical measure used to assess BMI in paediatric patients considering a patient’s BMI and comparing it to reference values for the same age and sex) and mean percent change in BMI. A reduction in BMI Z score of 0·2 points or more has been defined as clinically important weight loss associated with cardiometabolic improvements. [6]
  • 2025-02-05: update guideline
  • 2024-03-05: Annual Review - No criteria changes
  • 2023-02-27: Annual review - No criteria changes
  • 2022-08-11: Added new indication for Bardet-Biedl syndrome. Separated PA criteria from NF criteria. Added additional requirements for submission of MR for NF criteria in initial and reauth. Updated background and references.
  • 2022-06-09: Removed submission of medical records and/or paid claims requirement from prior authorization criteria
  • 2022-01-10: Annual review - No criteria changes
  • 2021-03-30: Updated guideline name and type to say prior authorization, non-formulary (PA, NF).
  • 2021-02-09: New Program