Aetna considers metreleptin (Myalept) medically necessary for treatment of complications of leptin deficiency (serum leptin levels less than the 7th percentile of normal values reported by the 3rd National Health and Nutrition Examination survey (less than 7.0 ng/mL in females and less than 3.0 ng/mL in males)) in persons with congenital generalized or acquired generalized lipodystrophy and concurrent type 2 diabetes mellitus, hypertriglyceridemia as defined by fasting triglyceride concentrations greater than 300 mg/dL, or hyperinsulinemia as defined by fasting serum insulin greater than 20 uU/mL.

Metreleptin is considered experimental and investigational for all other indications, including all of the following:

• Complications of partial lipodystrophy
• Liver disease, including nonalcoholic steatohepatitis (NASH)
• HIV-related lipodystrophy
• Metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of congenital or acquired generalized lipodystrophy
• Generalized obesity not associated with leptin deficiency.

The U.S. Food and Drug Administration (FDA) has approved metreleptin (Myalept, Amylin Pharmaceuticals), an analog of leptin made through recombinant DNA technology, as replacement therapy to treat the complications of leptin deficiency, in addition to diet, in patients with congenital generalized or acquired generalized lipodystrophy.  

Generalized lipodystrophy is a condition associated with a lack of fat tissue. Patients with congenital generalized lipodystrophy are born with little or no fat tissue. Patients with acquired generalized lipodystrophy generally lose fat tissue over time. Because the hormone leptin is made by fat tissue, patients with generalized lipodystrophy have very low leptin levels. Leptin is known to regulate food intake and other hormones, such as insulin.

Patients with both types of generalized lipodystrophy often develop severe insulin resistance at a young age and may have diabetes mellitus that is difficult to control or hypertriglyceridemia that can lead to pancreatitis.

The safety and effectiveness of Myalept were evaluated in an open-label, single-arm study that included 48 patients with congenital or acquired generalized lipodystrophy who also had diabetes mellitus, hypertriglyceridemia, or elevated levels of fasting insulin. The trial showed reductions in HbA1c, fasting glucose, and triglycerides.

Anti-drug antibodies with neutralizing activity to leptin or metreleptin may develop, which could result in severe infections or loss of treatment effectiveness. T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with metreleptin. The FDA approved labeling advises that healthcare professionals should carefully consider the benefits and risks of treatment with metreleptin in patients with significant hematologic abnormalities or acquired generalized lipodystrophy. Metreleptin is contraindicated in patients with general obesity. Myalept is not approved for use in patients with HIV-related lipodystrophy or in patients with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of generalized lipodystrophy.

Because of the risks associated with the development of neutralizing antibodies and lymphoma, Myalept is available only through the Myalept Risk Evaluation and Mitigation Strategy (REMS) Program. Under this REMS program, prescribers must be certified with the program by enrolling in and completing training. Pharmacies must be certified with the program and only dispense Myalept after receipt of the Myalept REMS Prescription Authorization Form for each new prescription.

In clinical trials, the most common side effects observed in patients treated with metreleptin were hypoglycemia, headache, decreased weight, and abdominal pain.

Myalept is administered administer as a subcutaneous injection once daily. The recommended daily dosages in milligrams (mg) per kilogram (kg) of body weight are:

• Body weight 40 kg or less: starting dose 0.06 mg/kg/day, increase or decrease by 0.02 mg/kg to a maximum daily dose of 0.13 mg/kg.
• Males greater than 40 kg body weight: starting dose 2.5 mg/day, increase or decrease by 1.25 mg to 2.5 mg/day to a maximum dose of 10 mg/day.
• Females greater than 40 kg body weight: starting dose 5 mg/day, increase or decrease by 1.25 mg to 2.5 mg/day to a maximum dose of 10 mg/day.

The FDA approved labeling states that the safety and effectiveness of Myalept for the treatment of complications of partial lipodystrophy have not been established. The labeling also states that the safety and effectiveness of Myalept for the treatment of liver disease, including nonalcoholic steatohepatitis (NASH), have not been established. The labeling states that Myalept is not indicated for use in patients with HIV-related lipodystrophy, or in patients with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of congenital or acquired generalized lipodystrophy.

The labeling states that Myalept is contraindicated in patients with general obesity not associated with congenital leptin deficiency. The labeling explains that Myalept has not been shown to be effective in treating general obesity, and the development of anti-metreleptin antibodies with neutralizing activity has been reported in obese patients treated with Myalept. The labeling also states that Myalept is contraindicated in patients with prior severe hypersensitivity reactions to metreleptin or to any of the product components. Known hypersensitivity reactions have included urticaria and generalized rash

The FDA is requiring seven studies (post-marketing requirements) for Myalept, including a long-term prospective observational study (product exposure registry) of patients treated with metreleptin, a study to assess for the immunogenicity (antibody formation) of metreleptin, and an assessment and analysis of spontaneous reports of potential serious risks related to the use of metreleptin. Eight additional studies are being requested as post-marketing commitments.