Setmelanotide (Imcivree) Form

Setmelanotide (Imcivree™) is melanocortin-4 receptor pathway activator.
FDA Approved Indication(s) Imcivree is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndrome obesity due to: • Proopiomelanocortin (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) • Bardet-Biedl syndrome (BBS) Limitation(s) 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
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Imcivree is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Genetic Obesity Disorders (must meet all):

1. Diagnosis of obesity due to POMC deficiency, PCSK1 deficiency, LEPR deficiency, or BBS (see Appendix D);
2. Prescribed by or in consultation with an endocrinologist or expert in rare genetic disorders of obesity;

3. Member meets one of the following (a or b): a. Age ≥ 6 and < 18 years with one of the following weight percentiles for age on growth chart assessment (see Appendix D) (i or ii): i. POMC, PCSK1, or LEPR deficiency: > 95th percentile; ii. BBS: > 97th percentile;
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   CLINICAL POLICY Setmelanotide b. Age ≥ 18 years of age and body mass index (BMI) ≥ 30 kg/m2;

4. One of the following (a or b): a. Genetic testing confirms that variants in the following genes are interpreted as pathogenic, likely pathogenic, or of uncertain significance (i, ii, or iii): i. POMC; ii. PCSK1; iii. LEPR; b. Diagnosis of BBS is confirmed clinically per Beales criteria (see Appendix D);
5. Documentation of baseline weight (in past 60 days) in kilograms;
   6. Documentation of creatinine clearance ≥ 15 mL/min/1.73 m2;
   7. If member has had prior gastric bypass surgery, member meets one of the following (a or b): a. Member has not had > 10% weight loss from baseline pre-operative weight; b. Member has regained weight after an initial response to surgery;
6. Documentation that member is actively enrolled in a weight loss program that involves a reduced calorie diet and increased physical activity adjunct to therapy;
7. Dose does not exceed any of the following (a and b): a. First 2 weeks (i or ii): i. Age ≥ 6 and < 18 years: 1 mg per day; ii. Age ≥ 18 years: 2 mg per day; b. Maintenance: 3 mg per day. Approval duration:
   POMC, PCSK1, or LEPR deficiency – 4 months BBS – 12 months B. Other diagnoses/indications (must meet 1 or 2):
8. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
9. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Genetic Obesity Disorders (must meet all):

10. Member meets one of the following (a or b): Page 2 of 7

    CLINICAL POLICY Setmelanotide a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

11. Member is responding positively to therapy as evidenced by one of the following (a, b, or c): a. Initial re-authorization for POMC, PCSK1, or LEPR deficiency: After 12-16 weeks of treatment, reduction of at least 5% of baseline body weight or 5% of baseline BMI; b. Initial re-authorization for BBS: After 1 year of treatment, reduction of at least 5% of baseline body weight or 5% of baseline BMI; c. Subsequent re-authorizations for all indications: Maintenance of ≥ 5% reduction in weight or BMI compared with baseline;
12. If request is for a dose increase, new dose does not exceed 3 mg per day. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
13. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

14. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents; B. Obesity disorders not caused by POMC, PCSK1, or LEPR deficiency or by BBS; C. Obesity disorder in patients with POMC, PCSK1, or LEPR gene variants that are interpreted as benign or likely benign.
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    CLINICAL POLICY Setmelanotide IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key BBS: Bardet-Biedl syndrome BMI: body mass index FDA: Food and Drug Administration LEPR: leptin receptor
    Appendix B: Therapeutic Alternatives
    Not applicable PCSK1: proprotein convertase subtilisin/kexin type 1 POMC: pro-opiomelanocortin VUS: variant of uncertain significance
    Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information
    • Body mass index calculator: https://globalrph.com/medcalcs/body-mass-index-bmi/
    • CDC Clinical Growth Charts from 3rd to 97th percentiles:
    o 2 to 20 years: Boys Stature-for-age and Weight-for-age percentiles https://www.cdc.gov/growthcharts/data/set2clinical/cj41c071.pdf o 2 to 20 years: Girls Stature-for-age and Weight-for-age percentiles https://www.cdc.gov/growthcharts/data/set2clinical/cj41c072.pdf • A clinical diagnosis of BBS is confirmed using Beales criteria. There must be presence of at least 4 primary features, OR 3 primary and 2 secondary features:
    o Primary features: rod-cone dystrophy, polydactyly, obesity, learning disabilities, hypogonadism in males, renal anomalies
    o Secondary features: speech disorder/delay, strabismus/cataracts/astigmatism, brachydactyly/syndactyly, developmental delay, polyuria/polydipsia (nephrogenic diabetes insipidus), ataxia/poor coordination/imbalance, mild spasticity (especially lower limbs), diabetes mellitus, dental crowding/hypodontia/small roots/high arched palate, left ventricular hypertrophy/congenital heart disease, hepatic fibrosis V. Dosage and Administration Indication Dosing Regimen Obesity due to POMC, PCSK1, or LEPR deficiency or due to BBS ≥ 12 years and older: 2 mg SC once daily for 2 weeks; if tolerated, titrate up to 3 mg SC once daily Age 6 to 12 years: 1 mg SC once daily for 2 weeks; if tolerated, titrate up to 3 mg SC once daily Maximum Dose 3 mg/day VI. Product Availability Vial: 10 mg/mL (1 mL multi-dose) Page 4 of 7

    CLINICAL POLICY Setmelanotide VII.