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Date Printed: December 18, 2017: 03:24 PM

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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J2000-12

Original Effective Date: 06/15/14

Reviewed: 05/13/15

Revised: 11/01/15

Subject: Metreleptin (Myalept™) Injection

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates
           

DESCRIPTION:

Lipodystrophy is a group of rare disorders characterized by the loss of body fat and resulting metabolic abnormalities; to a large extent, the magnitude and distribution of fat loss determine the associated co-morbidities. Individuals affected by lipodystrophy are predisposed to insulin resistance, hyperglycemia, type 2 diabetes, dyslipidemia, and hypertriglyceridemia Since the key characteristic of lipodystrophy is the selective absence of adipose tissue (primarily subcutaneous), the levels of adipocyte hormones can be altered. The best characterized of these hormones is leptin, with low leptin levels typically observed in patients with lipodystrophy; however, levels of other adipocytokines, such as adiponectin, are also lower in lipodystrophy.

Lipodystrophy is classified on the basis of the extent or pattern of the fat loss (generalized or partial) and if the disease is genetic or acquired. This classification scheme yields four major lipodystrophy subtypes: congenital generalized lipodystrophy (CGL), acquired generalized lipodystrophy (AGL), familial partial lipodystrophy (FPL), and acquired partial lipodystrophy (APL). Diagnosis relies largely on recognition of the core clinical characteristic of lipodystrophy: loss or absence of subcutaneous body fat in a partial or generalized fashion. This characteristic is highly recognizable in those with generalized lipodystrophy. Outside of cases of HAART-induced lipodystrophy in HIV-infected individuals, lipodystrophy is an extremely rare disease.

The primary goal of treatment in lipodystrophy is to prevent morbidity and mortality from diabetes mellitus, acute pancreatitis from extreme hypertriglyceridemia, and cirrhosis from long-standing hepatic steatosis. Current therapeutic options for the metabolic management of lipodystrophy consist of lifestyle modifications (diet and exercise) and conventional antihyperglycemic and lipid-lowering medications.

Metreleptin (Myalept) was approved by the U.S. Food and Drug Administration (FDA) in February 2014 as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in those with congenital or acquired generalized lipodystrophy. The safety and effectiveness of metreleptin for the treatment of complications of partial lipodystrophy or liver disease (including nonalcoholic steatohepatitis) has not been established. Additionally, metreleptin is not indicated for use in those with HIV-related lipodystrophy or in those with metabolic disease without concurrent evidence of generalized lipodystrophy.

Metreleptin is a recombinant human leptin analog that binds to and activates the human leptin receptor (ObR), which belongs to the Class I cytokine family of receptors that signals through the JAK/STAT transduction pathway. Native human leptin is a hormone predominately secreted by adipose tissue that regulates energy homeostasis and metabolic function. Circulating levels of leptin closely correlate with the amount of adipose tissue present; therefore, in generalized lipodystrophy, a resulting leptin deficiency contributes to excess caloric intake, which exacerbates the metabolic abnormalities of the disease.

The safety and efficacy of metreleptin were evaluated in an open-label, single-arm study of 48 individuals (median age = 15 years; range, 1—68 years) with either congenital or acquired generalized lipodystrophy and diabetes mellitus, hypertriglyceridemia, and/or increased fasting insulin. Metreleptin treatment resulted in reductions in HbA1c, fasting glucose, and triglycerides from baseline values. At 12 months, patients receiving metreleptin (n = 35) had a mean decrease of 2% from their mean baseline HbA1c of 8.7%. The mean baseline fasting glucose (n = 37) was 174 mg/dl, and the mean reduction was 49 mg/dl. The median baseline fasting triglycerides (n = 36) was 348 mg/dl, which decreased by a median of 185 mg/dl. The weighted average daily dose for patients weighing > 40 kg was 2.6 mg/day SC for males and 4.6 mg/day for females during the first year of therapy and 3.2 mg/day (males) and 6.3 mg (females) over the entire study period. The median treatment duration was 2.7 years (range, 3.6 months—10.9 years). Adverse events with the greatest incidence (13%) related to metreleptin in clinical trial included headache, hypoglycemia, and decreased weight (6/48 subjects).

The FDA has required a Risk Evaluation and Mitigation Strategy for metreleptin due to the potential for serious side effects, including anti-metreleptin antibodies with neutralizing activity and lymphoma.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

Initiation of metreleptin injection meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with either congenital or acquired generalized lipodystrophy

2. Member has a laboratory documented leptin deficiency defined as:

a. Females: Less than 12.0 ng/mL

b. Males: Less than 8.0 ng/mL

c. Children age 6 months – 5 years: Less than 6 ng/mL

3. Member has ONE of the following

a. Diabetes defined as ONE of the following:

i. Fasting plasma glucose greater than or equal to 126 mg/dL

ii. 2-hour plasma glucose greater than or equal to 200 mg/dL following a 75 gram oral glucose load

iii. Symptoms of hyperglycemia (or hyperglycemic crisis) AND a random plasma glucose greater than or equal to 200 mg/dL

b. Fasting insulin greater than 30 μU/mL

c. Fasting hypertriglyceridemia greater than 200 mg/dL

d. Postprandial hypertriglyceridemia greater than 500 mg/dL

4. Dose does not exceed 10 mg daily

Duration of approval: 1 year

Continuation of metreleptin injection meets the definition of medical necessity when ALL of the following criteria are met:

1. Member has met Florida Blue’s initiation criteria or was previously approved by another health plan

2. Member demonstrates a beneficial response to treatment with metreleptin

3. Dose does not exceed 10 mg daily

Duration of approval: 1 year

Metreleptin is not considered a medical necessity for members with partial lipodystrophy or HIV-related lipodystrophy.

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved

• Weight greater than 40 kg: 2.5 mg/day (males), 5 mg/day (females) SQ injection; titrate to 10 mg/day

• Weight 40 kg or less: 0.06 mg/kg/day SQ injection; titrate to 0.13 mg/kg/day

Dose Adjustments

• Adjust dose based on clinical response: 1.25-2.5 mg/day if weight is greater than 40 kg; 0.02 mg/kg/day if weight is 40 kg or less

Drug Availability

• Sterile 11.3 mg vial to deliver 5 mg/mL when reconstituted with 2.2 mL of preservative-free water for injection.

PRECAUTIONS:

Boxed Warning

• Risk of lymphoma

• Risk of anti-metreleptin antibodies with neutralizing activity

Contraindications

• General obesity not associated with congenital leptin deficiency

• Hypersensitivity to metreleptin

Precautions/Warnings

• Anti-metreleptin antibodies with neutralizing activity: Could inhibit endogenous leptin action and/or result in loss of efficacy; test for neutralizing antibodies if severe infections or loss of efficacy

• T-cell lymphoma

• Hypoglycemia

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J3590

Unclassified biologics

ICD-10 Diagnoses Codes That Support Medical Necessity (Effective 10/01/15)

E88.1

Lipodystrophy, not elsewhere classified

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

DEFINITIONS:

None

RELATED GUIDELINES:

None

OTHER:

None

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2015 [cited 2015 Apr 3]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  2. Bristol Myers Squibb. Myalept (metreleptin) subcutaneous injection. 2014 [cited 2015 Apr 3]. Available from: http://packageinserts.bms.com/pi/pi_myalept.pdf?bcsi_scan_df00db2a5f4c15a6=0&bcsi_scan_filename=pi_myalept.pdf /.
  3. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2015 [cited 2015 Apr 3]. Available from: http://www.clinicalpharmacology.com/.
  4. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2015 Apr 3]. Available from: http://clinicaltrials.gov/.
  5. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2015 Apr 3]. Available from: http://www.thomsonhc.com/.
  6. Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004; 350(12):1220-34.
  7. Herranz P1, de Lucas R, Pérez-España L, Mayor M. Lipodystrophy syndromes. Dermatol Clin. 2008;26(4):569-78.
  8. Mantzoros CS. W(h)ither metreleptin for lipodystrophy and the metabolic syndrome? Endocr Pract. 2010;16(2):162-6.
  9. Oral EA, Chan JL. Rationale for leptin-replacement therapy for severe lipodystrophy. Endocr Pract. 2010;16(2):324-33.
  10. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2015 [cited 2015 Apr 3]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 05/13/15.

GUIDELINE UPDATE INFORMATION:

06/15/14

New Medical Coverage Guideline.

06/15/15

Review and revision of guidelines; consisting of position statement, updating references.

11/01/15

Revision: ICD-9 Codes deleted.

Date Printed: December 18, 2017: 03:24 PM