Regulatory Decision Summary for Myalepta

The purpose of this submission was to seek market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Myalepta (metreleptin for injection) for the treatment of complications due to leptin deficiency in lipodystrophy (LD) patients. After evaluation of the submitted data package, Health Canada authorized Myalepta as an adjunct to diet as a replacement therapy to treat the complications of leptin deficiency in LD patients:

• With confirmed congenital generalised LD (Berardinelli-Seip) syndrome or acquired generalised LD (Lawrence syndrome) in adults and children 2 years of age and above.

• With confirmed familial partial LD (PL) or acquired PL (Barraquer-Simons syndrome), in adults and children 12 years of age and above with persistent significant metabolic disease for whom standard treatment have failed to achieve adequate metabolic control.

Lipodystrophy (LD) syndromes are a group of rare heterogeneous disorders characterized by a loss of fat that causes a decrease in a hormone called leptin. The loss of leptin leads to metabolic abnormalities. LD syndromes are categorized into four major subtypes: congenital generalized lipodystrophy (GL), acquired GL, familial partial lipodystrophy (PL), and acquired PL. This is a chronic and progressive disease, with no cure, and is associated with increased morbidity and mortality, as well as impaired quality of life.

Authorization was primarily based on one single-arm, open-label study. The study enrolled leptin-deficient patients with congenital or acquired GL or familial or acquired PL and had at least one of the following three metabolic abnormalities: (1) diabetes mellitus, or (2) fasting insulin concentration >30µU/mL, or (3) fasting triglyceride concentration >2.26 mmol/L or postprandially elevated triglycerides >5.65 mmol/L.

The co-primary efficacy endpoints were absolute change from baseline in HbA1c at Month 12 and relative (%) change from baseline in fasting serum triglycerides at Month 12. A clinically meaningful metreleptin treatment benefit was observed based on within-patient changes from baseline for GL patients (n = 61) and a group of PL patients with more severe metabolic disease at baseline (n = 31).

The most commonly reported adverse events were weight decreased (17%), hypoglycaemia (14%), and fatigue (7%) .

Metreleptin is to be administered subcutaneously once daily (QD) at the same time every day. The recommended daily dose of Myalepta is based on body weight. For patients ≤40 kg, a starting daily dose of 0.06 mg/kg is recommended. For male patients >40 kg, a starting daily dose of 2.5 mg and for female patients >40 kg, a starting daily dose of 5 mg is recommended. Based on clinical response or other considerations, the dose may be decreased or increased. View the Product Monograph for more details.

Overall, based on the data evaluated as part of this submission, the benefit-risk profile of Myalepta, when used as per the recommended dosing regimen, is considered favourable for treating complications of leptin deficiency in LD patients who are 2 years of age or older and who have confirmed GL (congenital or acquired), or in patients 12 years of age or older with confirmed PL (familial or acquired), who have persistent significant metabolic disease and for whom standard treatments have failed to achieve adequate metabolic control.

An updated Risk Management Plan (RMP) for Myalepta was reviewed by Health Canada and considered acceptable. Risks have been communicated in the approved Product Monograph and will continue to be monitored post market as outlined in the Risk Management Plan, with routine and non-routine pharmacovigilance activities.

The chemistry and manufacturing information submitted for Myalepta has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

For further details about Myalepta, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.