The US Food and Drug Administration’s (FDA) Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) has recommended AstraZeneca and Bristol-Myers Squibb’s (BMS) investigational medicine metreleptin for the treatment of paediatric and adult patients with generalised lipodystrophy (LD).
FDA panel recommends AstraZeneca and BMS’ metreleptin for generalised lipodystrophy click here for story
Metreleptin, an analog of the human hormone leptin, is a unique potential therapy for certain metabolic disorders in patients with rare forms of inherited or acquired lipodystrophy. Lipodystrophy is a very rare condition characterized by loss of subcutaneous fat.
Metreleptin is being studied as a potential therapy for certain metabolic disorders in patients with inherited or acquired lipodystrophy. Metreleptin is believed to work by reducing fat accumulation in organs, caused by the disease, thereby improving insulin sensitivity. Clinical studies have been conducted by investigators at the National Institutes of Health (NIH) and other academic institutions in the US, Europe, and Japan to determine whether metreleptin can improve glycemic control and hypertriglyceridemia in patients with lipodystrophy.
In April 2012, Amylin completed its Biologics License Application (BLA) for metreleptin to treat diabetes and/or hypertriglyceridemia (high levels of triglycerides in the bloodstream) in patients with rare forms of lipodystrophy and requested Priority Review by the FDA.
If approved, metreleptin would be the first therapy indicated specifically for the treatment of diabetes and/or hypertriglyceridemia in patients with inherited or acquired lipodystrophy, and the first approved therapeutic use of a leptin analog.
Lipodystrophy is a life-threatening, “ultra orphan” rare disease that is estimated to impact a few thousand people worldwide, often with an early age of onset, for which there is a significant unmet medical need. There are currently no approved drugs that treat the underlying cause of the disease.
Fat tissue is a major endocrine organ producing important metabolic hormones such as leptin. People with lipodystrophy lack the required fat tissue for normal metabolic function. This can be partial, affecting select areas of the body, or generalized, affecting nearly the entire body. A lack of fat tissue can lead to relative deficiency of leptin.
Without adequate leptin function, the metabolic system, which regulates food intake and the storage and break-down of dietary fat and carbohydrates, falls out of balance. As a result, fat accumulates in the blood and organs such as liver and muscle, which can lead to life-threatening complications including insulin-resistant diabetes, hypertriglyceridemia (high levels of triglycerides in the bloodstream), acute pancreatitis, and hepatic steatosis or steatohepatitis, also known as fatty liver disease. There are no approved drugs that address the underlying relative leptin deficiency that is believed to contribute in large part to the metabolic abnormalities that occur in lipodystrophy. Currently available therapies for diabetes and hypertriglyceridemia are often rendered marginally effective due to the severity of the condition.