Effective Date

Date of Origin 

01-01-2026            

Myalept®

(metreleptin)

Subcutaneous injection

As an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy

Limitations of Use:

• The safety and effectiveness of Myalept for the treatment of complications of partial lipodystrophy have not been established.
• The safety and effectiveness of Myalept for the treatment of liver disease, including nonalcoholic steatohepatitis (NASH), have not been established.
• Not indicated for use in patients with HIV-related lipodystrophy.
• Not indicated for use in patients with metabolic disease, without concurrent evidence of generalized lipodystrophy.

1

Lipodystrophy

Lipodystrophy is a rare, heterogeneous group of syndromes characterized by the complete or partial loss or absence of subcutaneous adipose tissue. The loss or absence of adipose tissue results in decreased levels of leptin, which is an important hormone regulating appetite. Lipodystrophy is often, although not always, accompanied by metabolic abnormalities, including insulin resistance, diabetes mellitus, hepatic steatosis or steatohepatitis, and dyslipidemia.(2,3) Metabolic abnormalities associated with lipodystrophy can be severe and lead to substantial comorbidities, including acute pancreatitis (due to severe hypertriglyceridemia), hepatic cirrhosis, and premature cardiovascular disease.(2-5)

Lipodystrophy can generally be classified based on extent or pattern of fat loss (generalized or partial) and whether the disease is genetic or acquired. There are 4 major lipodystrophy subtypes: congenital generalized lipodystrophy (CGL), acquired generalized lipodystrophy (AGL), familial partial lipodystrophy (FPL), and acquired partial lipodystrophy (APL).(2-4)

Initial treatment of metabolic disturbances associated with lipodystrophy (e.g., diabetes, hypertriglyceridemia) is the same as in patients without lipodystrophy. Diabetes is treated with hyperglycemic drugs as well as insulin (although high doses are often required). Hypertriglyceridemia may be treated with statins, fibric acid derivatives, or omega-3 fatty acids. Individuals with CGL and AGL are encouraged to maintain a healthy weight by following a low-fat diet and engaging in regular exercise. If metabolic disturbances persist, metreleptin is recommended, along with careful monitoring, in these patients.(2,3,5)

Efficacy

Metreleptin is a recombinant human leptin analog that functions by binding to and activating the human leptin receptor which studies suggest causes an increase in insulin sensitivity and a reduction in food intake.(1)

The efficacy of metreleptin was evaluated in an open label single arm study of 48 patients with congenital (n=32) or acquired (n=16) generalized lipodystrophy who also had at least one of the metabolic abnormalities (diabetes mellitus, hypertriglyceridemia > 200 mg/dL, and/or increased fasting insulin [greater than or equal to 30 microU/mL]). At baseline, 37 (77%) patients had HbA1c values of 7% or greater, 19 (40%) had HbA1c values of 9% or greater, 33 (69%) had fasting plasma glucose values of 126 mg/dL or greater, 17 (35%) had fasting triglyceride values of 500 mg/dL or greater, and 11 (23%) had fasting triglyceride values of 1000 mg/dL or greater. The metreleptin treatment duration was 3.6 months to 10.9 years (median = 2.7 years) and metreleptin was administered either once or twice daily. At year 1, patients treated with metreleptin had mean/median reductions in HbA1c (-2%), fasting glucose (-49 mg/dL), and triglycerides (-55%). Concomitant anti-hyperglycemic and lipid-altering medications dosing regimens were not held constant throughout the study.(1)

Safety

Myalept has the following boxed warning for risk of anti-metreleptin antibodies with neutralizing activity and risk of lymphoma:(1)

• Anti-metreleptin antibodies with neutralizing activity have been identified in patients treated with Myalept. The consequences are not well characterized but could include inhibition of endogenous leptin action and loss of Myalept efficacy. Worsening metabolic control and/or severe infection have been reported. Test for anti-metreleptin antibodies with neutralizing activity in patients who develop severe infections or show signs suspicious for loss of efficacy during Myalept treatment
• T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with Myalept. Carefully consider the benefits and risks of treatment with Myalept in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy
• Myalept is available only through a restricted program called the Myalept REMS Program

Myalept has the following contraindications:(1)

• General obesity not associated with congenital leptin deficiency
• Hypersensitivity to Myalept

1

Myalept prescribing information. Aegerion Pharmaceuticals, Inc. March 2024.

2

Handelsman Y, Oral EA, Bloomgarden ZT, et al. The clinical approach to the detection of lipodystrophy - an AACE consensus statement. Endocr Pract. 2013;19(1):107-116. doi:10.4158/endp.19.1.v767575m65p5mr06

3

Brown RJ, Araujo-Vilar D, Cheung PT, et al. The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline. Journal of Clinical Endocrinology & Metabolism 2016;101(12):4500-4511. doi:10.1210/jc.2016-2466

4

Araújo-Vilar D, Santini F. Diagnosis and treatment of lipodystrophy: a step-by-step approach. J Endocrinol Invest. 2019;42(1):61-73. doi:10.1007/s40618-018-0887-z

5

National Organization for Rare Disorders (NORD). The Physician's Guide to Lipodystrophy Disorders; 2012. https://www.rareconnect.org/uploads/documents/the-physician-s-guide-to-lipodystrophy-disorders.pdf

Myalept

metreleptin for subcutaneous inj

11.3 MG

M ; N ; O ; Y

N

Myalept

metreleptin for subcutaneous inj

11.3 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

PA

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met: 

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. 1. 1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
      2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
   2. ALL of the following:
      1. The patient has a diagnosis of congenital generalized lipodystrophy (CGL) or acquired generalized lipodystrophy (AGL) AND
      2. The patient has a leptin deficiency confirmed by laboratory testing (i.e., less than 12 ng/mL) prior to initiating the requested agent AND
      3. The patient has at least ONE of the following complications related to lipodystrophy:
         1. Diabetes mellitus OR
         2. Hyperinsulinemia (i.e., greater than or equal to 30 microU/mL) OR
         3. Hypertriglyceridemia (i.e., greater than or equal to 200 mg/dL) AND
      4. The patient has had baseline HbA1c, triglycerides, and fasting insulin levels measured prior to initiating the requested agent AND
      5. The patient has tried and had an inadequate response to the maximum tolerable dose of a conventional agent for complications related to lipodystrophy OR
   3. The patient has another FDA labeled indication for the requested agent and route of administration AND
2. BOTH of the following:
   1. The patient has had an inadequate response to lifestyle modification (i.e., diet modification and exercise) AND
   2. The patient will continue lifestyle modifications with the requested agent AND
3. The patient does NOT have any of the following limitations of use for the requested agent:
   1. Partial lipodystrophy
   2. Liver disease (including non-alcoholic steatohepatitis [NASH] or metabolic associated steatohepatitis [MASH])
   3. HIV-related lipodystrophy
   4. Metabolic disease (e.g., diabetes mellitus, hypertriglyceridemia) without evidence of generalized lipodystrophy AND
4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent AND
6. The requested quantity (dose) is within FDA labeled dosing for the requested indication

Length of Approval: 12 months

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process (Note: patients not previously approved for the requested agent will require initial evaluation review) AND
2. The patient has had clinical benefit with the requested agent AND
3. The patient will continue lifestyle modifications (i.e., diet and exercise) with the requested agent AND
4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent AND
6. The requested quantity (dose) is within FDA labeled dosing for the requested indication

Length of Approval: 12 months