AstraZeneca and Bristol-Myers Squibb Company announced the US Food and Drug Administration’s (FDA) Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) has recommended the investigational medicine metreleptin for the treatment of paediatric and adult patients with generalised lipodystrophy (LD). Specifically, EMDAC determined by a vote of 11 to one that there is substantial evidence that the benefits of metreleptin exceed the risks for the treatment of paediatric and adult patients with generalised lipodystrophy.
EMDAC did not recommend metreleptin in patients with partial LD for the indication currently proposed, by a vote of two to 10. AstraZeneca and BMS remain committed to pursuing metreleptin for treatment in patients with metabolic disorders associated with partial LD. The companies acknowledge the committee’s feedback and will continue to work with the FDA to identify the appropriate patients with partial LD who may benefit from metreleptin.
The FDA is not bound by the EMDAC’s recommendation but will take it into consideration when reviewing the Biologics License Application (BLA) for metreleptin.
LD is a group of rare syndromes often associated with severe metabolic abnormalities and significant morbidity and mortality. Metreleptin is being reviewed by the FDA as a treatment of paediatric and adult patients with generalised lipodystrophy (LD) or metabolic disorders associated with partial LD, including hypertriglyceridemia and/or diabetes mellitus inadequately controlled on a current therapy, and/or evidence of hepatic steatosis (fatty liver disease).
The Prescription Drug User Fee Act (PDUFA) goal date for metreleptin is February 24, 2014. There are no therapies approved by the FDA to treat patients with rare forms of LD (not including HIV-associated LD).
The EMDAC based its recommendations on a review of data from the metreleptin clinical development programme for LD that supported the BLA submission, including pivotal efficacy and safety data from two open-label, investigator-sponsored National Institutes of Health (NIH) studies, as well as important supplemental efficacy and safety data on investigational metreleptin from an additional open-label expanded access study, FHA101.
The first clinical study of investigational metreleptin was initiated in 2000 by investigators at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of NIH. The open-label, investigator-sponsored pilot study was designed to evaluate the safety and efficacy of investigational metreleptin administration in patients with rare forms of generalised or partial LD and did not include patients with HIV-associated LD. Based on the efficacy data in the pilot study, a long-term, open-label clinical trial was initiated to determine the safety and efficacy of investigational metreleptin for improving metabolic abnormalities in patients with LD, and is currently ongoing.
Metreleptin, an investigational recombinant analog of the human hormone leptin, has received orphan designation from the US FDA and EMA. Metreleptin is being evaluated for the treatment of paediatric and adult patients with generalised LD or metabolic disorders associated with partial LD, including hypertriglyceridemia and/or diabetes mellitus inadequately controlled on a current therapy, and/or evidence of hepatic steatosis (fatty liver disease).
Dedicated to addressing the global burden of diabetes by advancing individualised patient care, AstraZeneca and Bristol-Myers Squibb are working in collaboration to develop and commercialise a versatile portfolio of innovative treatment options for diabetes and related metabolic disorders that aim to provide treatment effects beyond glucose control.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases.
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.