FDA approves Myalept for rare metabolic disease

FDA approved metreleptin for injection (Myalept, Amylin Pharmaceuticals) 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 regulates 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 inflammation of the pancreas.

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.

Myalept, a recombinant analogue of human leptin, has been approved with a Medication Guide and instructions for use that provides patients with important information about the medication. The guide will be distributed each time a patient fills a prescription.

In addition, Myalept is available only through the Myalept Risk Evaluation and Mitigation Strategy (REMS) Program due to the risks associated with the development of neutralizing antibodies and lymphoma. Pharmacies must be certified with the program and only dispense Myalept after receipt of the Myalept REMS Prescription Authorization Form for each new prescription.

“The FDA approval of Myalept is a movement toward improving the quality of life for individuals that experience the complications of complications of leptin deficiency,” said Abimbola Farinde, PharmD, MS, who serves on the faculty at Columbia Southern University, Orange Beach, Ala.

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, and/or elevated levels of fasting insulin. The trial showed reductions in HbA_1c, fasting glucose, and triglycerides. 

Antidrug antibodies with neutralizing activity to leptin and/or Myalept 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 Myalept, so healthcare professionals should carefully consider the benefits and risks of treatment with Myalept in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy. Myalept is contraindicated in patients with general obesity.

Hypoglycemia, headache, decreased weight, and abdominal pain were the most common side effects observed in patients taking Myalept in clinical trials. 

FDA is requiring 7 post-marketing studies for Myalept, including a long-term prospective observational study (product exposure registry) of patients treated with Myalept, a study to assess for the immunogenicity of Myalept, and an assessment and analysis of spontaneous reports of potential serious risks related to the use of Myalept. Eight additional studies are being requested as post-marketing commitments.