General Information

Myalept (metreleptin for injection) is a recombinant human leptin analog for injection that binds to and activates the leptin receptor.

Myalept is specifically indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy.

Myalept is supplied as a solution for subcutaneous injection. Myalept should be administered as a subcutaneous injection once daily after the lyophilized cake is reconstituted with Bacteriostatic Water for Injection (BWFI) or preservative-free sterile Water for Injection (WFI). 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

Mechanism of Action

Myalept (metreleptin for injection) is a recombinant human leptin analog for injection that binds to and activates the leptin receptor. Adipocytes store lipids to meet the fuel requirements of non-adipose tissues during fasting. In patients with generalized lipodystrophy, the deficiency of adipose tissue leads to hypertriglyceridemia and ectopic deposition of fat in non-adipose tissues such as liver and muscle, contributing to metabolic abnormalities including insulin resistance. Native leptin is a hormone predominantly secreted by adipose tissue that informs the central nervous system of the status of energy stores in the body. In patients with generalized lipodystrophy, leptin deficiency, resulting from the loss of adipose tissue, contributes to excess caloric intake, which exacerbates the metabolic abnormalities. Myalept exerts its function by binding to and activating the human leptin receptor (ObR), which belongs to the Class I cytokine family of receptors that signals through the JAK/STAT transduction pathway.

Side Effects

Adverse events associated with the use of Myalept may include, but are not limited to, the following:

• headache
  hypoglycemia
  decreased weight
  abdominal pain

The Myalept drug label comes with the following Black Box Warning: 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 with severe infections or 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.

Clinical Trial Results

The FDA approval of Myalept was based on an open-label, single-arm study in 48 subjects with congenital or acquired generalized lipodystrophy and diabetes mellitus, hypertriglyceridemia, and/or increased fasting insulin. Myalept was administered subcutaneously either once daily or twice daily (in two equal doses). The weighted average daily dose for the 36 subjects with baseline body weight greater than 40 kg was 2.6 mg for males and 4.6 mg for females during the first year of treatment, and 3.2 mg for males and 6.3 mg for females over the entire study period. For the 12 subjects with baseline body weight less than 40 kg, the weighted average daily dose was 0.06 to 0.11 mg/kg (0.8-4.3 mg) over the entire study period. The median treatment duration was 2.7 years. Among 28 subjects with generalized lipodystrophy who had a baseline HbA1c 7% or greater and data available at Month 12, the mean (SD) baseline HbA1c was 9.3 (1.5)% and the mean reduction in HbA1c at Month 12 was 2.4%. Among 12 subjects with generalized lipodystrophy who had a baseline triglyceride level 500 mg/dL or greater and data available at Month 12, the median baseline triglyceride level was 1527 mg/dL and the median reduction in triglycerides at Month 12 was 1117 mg/dL.