ModifiedCentenePolicy CP PHAR.491

Setmelanotide (Imcivree)

Defines medical necessity criteria, initial and continued therapy requirements, dosing, exclusions, approval durations, coding implications, and provider documentation requirements for coverage of Imcivree (setmelanotide) across Commercial, HIM and Medicaid lines of business.

Policy Summary

PayerCentene

PolicySetmelanotide (Imcivree)

Policy CodePolicy CP PHAR.491

Change TypePediatric extension; indication and criteria revisions

Effective DateNov 25, 2020

Next Review Date

Key ActionProvider must submit office chart notes, lab results, genetic testing reports, baseline weight in kg (within past 60 days), and creatinine clearance documentation to support that member meets approval criteria.

POLICY UPDATE CHANGES

Added PCSK1-deficiency obesity and extended pediatric age down to 2 years (pediatric extension).

Revised growth chart percentile thresholds: POMC/PCSK1/LEPR deficiency to 95th percentile and BBS to 97th percentile.

Clarified that genetic variants in POMC, PCSK1, and LEPR must be interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS); variants classified as benign or likely benign are excluded.

Added creatinine clearance requirement >= 15 mL/min/1.73 m2.

Expanded initial approval duration from 12 weeks to 4 months for POMC/PCSK1/LEPR deficiency.

Added requirement for enrollment in a weight loss program for age >=6 years.

Updated contraindications to include hypersensitivity to setmelanotide or any of its excipients.

Updated coding references and HCPCS/J-code guidance (C9399, J3490) for informational purposes.

3FDA-indicated genetic causes covered (POMC, PCSK1, LEPR)

1FDA-indicated syndromic cause covered (BBS)

>=5%Required minimal weight/BMI reduction for response

15 mL/min/1.73 m2Minimum creatinine clearance required

Coverage Summary

Imcivree (setmelanotide) is covered with criteria aligned to FDA labeling and the prescribing information for reduction of excess body weight in patients with POMC, PCSK1, or LEPR deficiency and Bardet-Biedl syndrome (BBS). Coverage requires genetic testing confirmation of qualifying variants (pathogenic, likely pathogenic, or VUS), adherence to age and weight/BMI thresholds (including pediatric age/weight criteria and adult BMI thresholds), and limits consistent with the product labeling and policy scope.

Initial Therapy Criteria

Initial Approval Criteria

Imcivree is medically necessary when ALL of the following are met:

ref

Initial Dosing / Titration Requirements

Dosing/titration schema by age (must meet):

Initial Dosing / Titration Requirements - top level

Age >=12 years and older: 2 mg subcutaneous (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.
Age 2 to <6 years: 0.5 mg SC once daily for 2 weeks; if tolerated, titrate up to recommended maintenance dose as determined by body weight per the provided weight-based schedule.
Weight-based schedule defines stepwise increases per weight bands in prescribing information.
Maximum dose: Age >6 years: 3 mg/day; for <6 years follow weight-based regimen and FDA guidance for maximum recommended dose based on weight.3 mg/day for age >6 years

ref

Continuation Therapy (Reauthorization) Criteria

Continued Therapy (Reauthorization) Criteria

Continued therapy is approved when ALL of the following are met:

Continued Therapy - top level

Continuity of care: Member is currently receiving the medication via Centene benefit and previously met initial approval criteria OR member is in continuity of care per state/product regulations.
Documented clinical response
- POMC/PCSK1/LEPR initial response: 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.
- BBS initial response: For BBS: After 1 year of treatment, reduction of at least 5% of baseline body weight or 5% of baseline BMI.

Exclusions / Not Authorized Indications

Coverage is NOT authorized for the following (any):

Exclusions - top level

Non-POMC/PCSK1/LEPR/BBS obesity: Obesity disorders not caused by POMC, PCSK1, or LEPR deficiency or by Bardet-Biedl syndrome (BBS).
Non-FDA indications: Non-FDA approved indications not addressed in this policy are not authorized unless there is sufficient documentation per applicable off-label use policies (referenced policies).
Benign/likely benign variants excluded: Obesity disorder in patients with POMC, PCSK1, or LEPR gene variants interpreted as benign or likely benign is not authorized.

Applicable Codes

HCPCS / Drug administration coding referencedHCPCS

C9399	Unclassified or biologicals/drugs (informational)
J3490	Unclassified drugs (informational)

Provider Actions & Billing

Prior Authorization

Prior authorization required

Requests require prior authorization and must meet the policy's initial or continued therapy criteria, including age/weight thresholds, genetic confirmation, response thresholds, and dosing limits; approval durations differ by diagnosis and line of business.

Approval duration differs by diagnosis and line of business (e.g., POMC/PCSK1/LEPR deficiency: 4 months; BBS: Medicaid/HIM 12 months, Commercial 6 months or to renewal date)

Documentation Required

Submit supporting clinical documentation

Submit office chart notes and clinical data to demonstrate the member meets initial or continued therapy criteria.

Office chart notes

Clinical Evidence & References

Evidence includes Phase 3 trials demonstrating efficacy and safety of setmelanotide in individuals with POMC and LEPR deficiency and trials in BBS (Lancet Diabetes Endocrinol. 2020). The policy references the Imcivree Prescribing Information (December 2024) for efficacy, safety, and dosing guidance and aligns response and reauthorization timepoints to those sources.

Background

Mechanism: Imcivree (setmelanotide) is a melanocortin-4 receptor pathway activator. FDA-approved indications include obesity due to POMC, PCSK1, or LEPR deficiency confirmed by genetic testing and Bardet-Biedl syndrome in patients 2 years of age and older. The policy aligns with FDA labeling and prescribing information, requiring genetic confirmation of qualifying variants and applying the age- and weight/BMI-based dosing and threshold criteria from the product label.

Definitions:

BBS — Bardet-Biedl syndrome

POMC — pro-opiomelanocortin

PCSK1 — proprotein convertase subtilisin/kexin type 1

LEPR — leptin receptor

VUS — variant of uncertain significance

Revision History

02.25material_changeLatest

Added PCSK1-deficiency obesity to FDA-approved indications and extended pediatric age down to 2 years (pediatric extension). P&T Approval Date = 02.25; references updated. (Moved BBS clinical criteria into initial criteria noted subsequently.)

01.05.21material_change

Updated policy per FDA labeling: added PCSK1-deficiency obesity; revised lower age limit from 12 years to 6 years; revised growth chart percentile threshold from 97th to 95th percentile for POMC/PCSK1/LEPR; clarified genetic variant interpretation (pathogenic, likely pathogenic, or VUS qualify; benign/likely benign excluded); added creatinine clearance requirement >= 15 mL/min/1.73 m2; added weight loss program requirement for age >=6 years; expanded initial approval duration from 12 weeks to 4 months; updated specialist requirement; exclusions clarified.

Policy Summary

PayerCentene

PolicySetmelanotide (Imcivree)

Policy CodePolicy CP PHAR.491

Change TypePediatric extension; indication and criteria revisions

Effective DateNov 25, 2020

Next Review Date

On This Page

Maintenance response: Subsequent re-authorizations for all indications: Maintenance of >=5% reduction in weight or BMI compared with baseline.>=5%

Dose increase constraint: If request is for a dose increase, the new dose must not exceed the FDA-approved maximum based on age/weight.

Genetic testing reports

Baseline weight in kilograms (within past 60 days)

Documentation of creatinine clearance (>= 15 mL/min/1.73 m2)

Documentation Required

Specialist involvement

Prescription must be by or in consultation with an endocrinologist or an expert in rare genetic disorders of obesity.

Step Therapy

Weight loss program requirement (age >=6)

For patients age 6 years and older, document active enrollment in a structured weight loss program as an adjunct to therapy; the program should include a reduced-calorie diet combined with increased physical activity.

Billing Rule

Use provided HCPCS/J-codes for claims

The policy references HCPCS/J-codes for informational purposes; providers should follow current professional coding guidance when submitting claims.

C9399
J3490

08.22revised

Revised creatinine clearance and positive response requirements per prescribing information; for POMC/PCSK1/LEPR deficiency, removed initial maintenance approval duration of 6 months as weight loss should be evaluated after 4 months per prescribing information.

02.24administrative

References reviewed and updated during 1Q 2024 annual review; P&T Approval Date = 02.24.

07.01.22administrative

Updated criteria to include new FDA approved indication of obesity due to BBS; revised creatinine clearance and positive response requirements per prescribing information; initial maintenance approval timing adjusted per PI.

02.21administrative

P&T Approval Date = 02.21 (references/revision log noted).

01.09.25administrative

Imcivree Prescribing Information (December 2024) referenced and accessed Jan 9, 2025; labeling supports FDA indications and age expansion to 2 years.

05.25material_change

For BBS diagnosis, moved the clinical criteria components of the Beales criteria into the initial criteria; updated contraindications to include hypersensitivity to setmelanotide or any of its excipients (updated per PI).