ModifiedmhnPolicy CP.PHAR.491

Setmelanotide (Imcivree) coverage for genetic/syndromic obesity

Defines medical necessity and prior authorization criteria for Imcivree (setmelanotide) for patients with POMC, PCSK1, LEPR deficiencies or Bardet-Biedl syndrome (BBS); applies to providers requesting coverage under the payer's commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicySetmelanotide (Imcivree) coverage for genetic/syndromic obesity

Policy CodePolicy CP.PHAR.491

Change TypeCriteria updated — new BBS indicationevaluation timing and approval durations revised

Effective DateNov 25, 2020

Next Review Date

Key ActionSubmit prior authorization with genetic confirmation or clinical BBS diagnosis, baseline weight, renal function, and specialist documentation to support approval.

SourceLink

POLICY UPDATE CHANGES

Added FDA-approved indication for obesity due to Bardet-Biedl syndrome (BBS) to policy criteria.

Revised creatinine clearance and positive response requirements per prescribing information.

For POMC, PCSK1, or LEPR deficiency, removed initial maintenance approval duration of 6 months and adjusted evaluation timing to 4 months.

For BBS initial criteria, added commercial language: '6 months or to the member's renewal date, whichever is longer'.

Added contraindication for hypersensitivity to setmelanotide or any of its excipients and extended pediatric indication to age ≥ 2 years per prescribing information.

Age ≥2minimum indicated age

BMI ≥30adult coverage threshold

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Coverage Criteria

Initial Therapy — Covered when ALL of the following are met.

Covered when ALL of the following are met:

Initial Approval - Genetic Obesity Disorders: 1) Diagnosis: (a) POMC, PCSK1, or LEPR deficiency confirmed by genetic testing demonstrating variants interpreted as pathogenic, likely pathogenic, or of uncertain significance; OR (b) Bardet-Biedl syndrome (BBS) confirmed clinically per Beales criteria as either (i) ≥4 primary features OR (ii) ≥3 primary features plus ≥2 secondary features.

Prescriber: 2) Medication is prescribed by or in consultation with an endocrinologist or an expert in rare genetic disorders of obesity.

Age and Weight/BMI thresholds: 3) Member meets one of the following: (a) Age ≥2 and <6 years with BMI ≥97th percentile for age and sex; (b) Age ≥6 and <18 years with weight percentile: >95th percentile for POMC/PCSK1/LEPR deficiency OR >97th percentile for BBS; (c) Age ≥18 years with BMI ≥30 kg/m2.

Minimum weight: 4) Weight ≥15 kg.

Baseline documentation: 5) Documentation of baseline weight in kilograms within the past 60 days.

Renal function: 6) Documentation of creatinine clearance ≥15 mL/min/1.73 m2.

Prior bariatric surgery: 7) If prior gastric bypass surgery, member meets one of: (a) has not had >10% weight loss from pre-operative baseline; OR (b) has regained weight after an initial response to surgery.

Behavioral program (age ≥6): 8) For age ≥6 years: documentation of active enrollment in a weight loss program involving reduced calorie diet and increased physical activity as adjunct to therapy.

Dose limits and titration: 9) Dose does not exceed the following: (a) Initial titration for first 2 weeks: age 2–<6 years = 0.5 mg/day; age 6–<12 years = 1 mg/day; age ≥12 years = 2 mg/day; (b) Maintenance: age 2–<6 years = FDA weight‑based maximum per prescribing information; age ≥6 years = 3 mg/day.

Continuation Therapy — Continued coverage when ALL of the following are met.

Continued coverage when ALL of the following are met:

Continued therapy eligibility: 1) Member is currently receiving the medication via the benefit or has previously met initial approval criteria; continuity of care provisions apply where state/product specific rules exist.

Positive response to therapy: 2) Member demonstrates a positive response as evidenced by: (a) For POMC, PCSK1, or LEPR deficiency — initial reauthorization after 12–16 weeks with ≥5% reduction from baseline body weight or baseline BMI; (b) For BBS — initial reauthorization after 1 year with ≥5% reduction from baseline body weight or BMI; (c) Subsequent reauthorizations for all indications — maintenance of ≥5% reduction in weight or BMI compared with baseline.≥5% weight/BMI reduction as described

Dose increase limits: 3) If a dose increase is requested, the new dose must not exceed: age 2–<6 years — FDA weight‑based maximum per prescribing information; age ≥6 years — 3 mg/day.

Updated Coverage Criteria Highlights — Policy criteria updated to include new indications and revise evaluation timing and approval durations.

Policy criteria were updated to include new indications and to revise evaluation timing and approval durations.

BBS initial approval duration: For Bardet‑Biedl syndrome (BBS) initial criteria, commercial line of business language added: approval for 6 months or to the member's renewal date, whichever is longer.6 months or to renewal date

POMC/PCSK1/LEPR evaluation timing: For POMC, PCSK1, or LEPR deficiency, the prior fixed 6‑month initial maintenance approval was removed and weight loss evaluation timing was revised to evaluate response at 4 months per prescribing information; requests for continued maintenance therapy may be approved using continued approval criteria.4 months

Contraindication and pediatric extension: Contraindication language was updated to include hypersensitivity to setmelanotide or any of its excipients; pediatric indication extended to age ≥2 years per prescribing information.

Coverage is not authorized for indications that are not FDA‑approved unless the request is supported by the payer's applicable off‑label use policy (see CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid). In addition, coverage is not authorized for obesity disorders that are not caused by POMC, PCSK1, or LEPR deficiency or by Bardet‑Biedl syndrome (BBS). Requests for patients with POMC/PCSK1/LEPR gene variants interpreted as benign or likely benign are also not authorized under this policy.

A documented hypersensitivity to setmelanotide or to any of its excipients is an explicit contraindication and the drug is not authorized for use in such patients, consistent with the prescribing information.

Use of setmelanotide for obesity disorders that are not caused by the specified genetic deficiencies (POMC, PCSK1, LEPR) or by BBS is considered not authorized (not medically necessary) under this policy unless the request meets the payer's off‑label use policy requirements.

Initial Therapy Criteria

Initial Therapy — Initial therapy criteria and dosing.

Initial therapy criteria and dosing:

Initial therapy nodes: 1) Diagnostic confirmation: POMC, PCSK1, or LEPR deficiency by genetic testing with variants interpreted as pathogenic, likely pathogenic, or VUS, OR clinical BBS confirmed by Beales criteria (≥4 primary OR ≥3 primary + ≥2 secondary). 2) Specialist involvement: prescribed by or in consultation with an endocrinologist or rare genetic obesity expert. 3) Age/weight/BMI thresholds and minimum weight: see initial criteria for age‑specific BMI/percentile cutoffs; weight ≥15 kg and baseline weight documented within 60 days. 4) Renal function: creatinine clearance ≥15 mL/min/1.73 m2. 5) Prior gastric bypass conditions and enrollment in weight‑loss program for age ≥6. 6) Dosing/titration: first 2 weeks titration (age 2–<6 = 0.5 mg/day; 6–<12 = 1 mg/day; ≥12 = 2 mg/day) and maintenance dosing per weight/FDA guidance with maximum 3 mg/day for age ≥6; weight‑based maintenance for age <6 per prescribing information.

Initial Therapy — Initial approval language updated for specific diagnoses and commercial lines of business.

Initial approval language updated for specific diagnoses and commercial lines of business.

BBS commercial approval language:

Continuation / Maintenance Criteria

Continued Therapy — Continued therapy requirements for genetic obesity disorders.

Continued therapy requirements for genetic obesity disorders:

Eligibility for continued therapy: 1) Member currently receiving medication via the benefit or previously met initial criteria; continuity of care rules apply where relevant.

Response evaluation timing and threshold: 2) Demonstrated positive response: For POMC/PCSK1/LEPR initial reauthorization after 12–16 weeks show ≥5% reduction from baseline body weight or BMI; for BBS initial reauthorization after 1 year show ≥5% reduction; subsequent reauthorizations require maintenance of ≥5% reduction versus baseline. Note: per updated criteria, POMC/PCSK1/LEPR weight loss evaluation timing may be aligned to 4 months per prescribing information for some requests.≥5% weight/BMI reduction as described

Dose limits for continued therapy: 3) Dose increases must not exceed age‑based maxima: age 2–<6 years — FDA weight‑based maximum per PI; age ≥6 years — 3 mg/day.

Coding

HCPCS Codes (informational)HCPCS

C9399	Unclassified drugs or biologicals
J3490	Unclassified drugs

Informational HCPCS CodesHCPCS

C9399	Unclassified drugs or biologicals
J3490	Unclassified drugs

Age and weight/BMI thresholds — pediatric and adult

Pediatric (age ≥2 to <6)BMI ≥ 97th percentile for age and sex (see growth chart assessment)

Pediatric (age ≥6 to <18) — monogenic deficienciesPOMC, PCSK1, or LEPR deficiency: weight for age > 95th percentile on growth chart assessment

Pediatric (age ≥6 to <18) — BBSBardet-Biedl syndrome (BBS): weight for age > 97th percentile on growth chart assessment

Adult (age ≥18)BMI ≥ 30 kg/m2

Minimum weight requirementWeight ≥ 15 kg (all ages)

Evaluation interval for weight loss

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must document genetic confirmation or clinical diagnosis of Bardet-Biedl syndrome (per Beales criteria) or pathogenic/likely pathogenic/uncertain variants in POMC, PCSK1, or LEPR as applicable, specialist prescribing or consultation (endocrinologist or rare genetic obesity disorder expert), and supporting clinical information including baseline measures.

Prior authorization required with documentation of genetic confirmation or clinical BBS diagnosis, specialist prescribing/consultation, and supporting documentation (office notes, lab results, genetic testing).
Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that member has met all approval criteria, including baseline weight (within past 60 days) and creatinine clearance ≥ 15 mL/min/1.73 m2.
Dose limits and age/weight requirements from policy must be met and documented.
For Commercial line of business for BBS initial criteria, standard approval language may be '6 months or to the member's renewal date, whichever is longer' per annual updates.

Definitions

Bardet-Biedl syndrome (BBS) — Beales criteria (policy definition)

Beales primary featuresAt least 3 primary features: rod-cone dystrophy, polydactyly, obesity, learning disabilities, hypogonadism in males, renal anomalies

Beales secondary features (require ≥2 when 3 primary also used)Speech disorder/delay; strabismus/cataracts/astigmatism; brachydactyly/syndactyly; developmental delay; polyuria/polydipsia (nephrogenic DI); 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

BBS diagnostic rule used in policyClinical BBS diagnosis requires either ≥4 primary features OR ≥3 primary plus ≥2 secondary features (Beales criteria)

Variant of uncertain significance (VUS)

DefinitionVariant of Uncertain Significance (VUS): a genetic variant whose association with disease risk is currently unclear or not definitively classified as pathogenic or benign

Background

Setmelanotide is a melanocortin‑4 receptor pathway activator approved for certain genetic and syndromic forms of early‑onset severe obesity, including obesity due to POMC, PCSK1, or LEPR deficiency and, as updated in this policy, obesity due to Bardet‑Biedl syndrome (BBS). The policy was updated to add the BBS indication, to extend the pediatric indication to age ≥ 2 years, and to include the prescribing information contraindication for hypersensitivity to setmelanotide or any of its excipients.

Step Therapy

Step	Requirement / Routing
1
If the drug label has changed within the last 6 months and the change is not yet reflected in this policy, follow the payer's formulary/no-coverage routing or non-formulary routing policies for the relevant line of business (see CP.CPA.190, HIM.PA.33, CP.PMN.255 for formulary/no-coverage; CP.CPA.190, HIM.PA.103, CP.PMN.16 for non-formulary). If the requested use is not listed in Section III and the label-change routing does not apply, refer to the off-label use policy for the relevant line of business (CP.CPA.09, HIM.PA.154, CP.PMN.53).

Step

Requirement / Routing

If the drug label has changed within the last 6 months and the change is not yet reflected in this policy, follow the payer's formulary/no-coverage routing or non-formulary routing policies for the relevant line of business (see CP.CPA.190, HIM.PA.33, CP.PMN.255 for formulary/no-coverage; CP.CPA.190, HIM.PA.103, CP.PMN.16 for non-formulary). If the requested use is not listed in Section III and the label-change routing does not apply, refer to the off-label use policy for the relevant line of business (CP.CPA.09, HIM.PA.154, CP.PMN.53).

Step	Note
1
Template changes were applied to other diagnoses/indications and the continued therapy section; specific step therapy requirements or additional step details are not present in this excerpt.

Quantity Limits

Setmelanotide (Imcivree) — dosing limits

Maximum maintenance dose (age ≥6)3 mg per day

Age <6 yearsMaintenance dose per FDA‑approved, weight‑based dosing regimen (see Section V dosing table) — follow weight-based maximum recommended dose

Initial titration dosesAge 2 to <6: 0.5 mg/day for first 2 weeks; Age 6 to <12: 1 mg/day for first 2 weeks; Age ≥12: 2 mg/day for first 2 weeks

Weight-based schedule examplesSection V provides specific daily doses by weight band (e.g., 15–<20 kg = 0.5 mg daily; 20–<30 kg titrate to 1 mg daily; etc.)