Advisory Committee recommends metreleptin for the treatment of pediatric and adult patients with generalized lipodystrophy; does not recommend for the treatment of partial lipodystrophy for the indication currently proposed
WILMINGTON, Del. & PRINCETON, N.J.--AstraZeneca (NYSE:AZN) and Bristol-Myers Squibb Company (NYSE:BMY) today announced the U.S. Food and Drug Administration's (FDA) Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) recommends the investigational medicine metreleptin for the treatment of pediatric and adult patients with generalized lipodystrophy (LD). Specifically, EMDAC determined by a vote of 11 to 1 that there is substantial evidence that the benefits of metreleptin exceed the risks for the treatment of pediatric and adult patients with generalized lipodystrophy.
EMDAC did not recommend metreleptin in patients with partial LD for the indication currently proposed, by a vote of 2 to 10. AstraZeneca and Bristol-Myers Squibb 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 pediatric and adult patients with generalized 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.
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 program 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.
About the NIH Metreleptin Studies
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 generalized 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 U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Metreleptin is being evaluated for the treatment of pediatric and adult patients with generalized 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.
LD is a group of rare syndromes often associated with severe metabolic abnormalities and significant morbidity and mortality. It is estimated to affect only a few thousand people worldwide. LD is heterogeneous in presentation and often occurs at an early age – during childhood or in early adulthood. There are several reasons for developing LD. In some patients, it is genetic, and in others it may be acquired for different reasons, including cases in which the immune system may attack and destroy existing fat tissue. Sometimes, clearly defined reasons for the development of the condition are unknown.
Whether genetic or acquired in origin, all forms of LD share a common pathophysiology: loss of fat tissue, especially fat under the skin. This loss of fat tissue, which causes a deficit in the hormone leptin, can vary from complete loss, or "generalized," to loss of fat in only some parts of the body, or "partial." Without enough fat tissue or leptin, the body's system for regulating energy use and storage falls out of balance. The resulting serious imbalance causes lipid to accumulate where it should not be found—such as in the liver and muscle—which may lead to severe metabolic abnormalities, primarily hypertriglyceridemia, severe insulin resistance with resultant hyperglycemia and type 2 diabetes, and hepatic steatosis (fatty liver disease).
The metabolic abnormalities in patients with LD are often difficult to control even with high doses of currently available diabetes and lipid-lowering therapies. These therapies are rendered less effective by the profound insulin resistance associated with LD. Moreover, these therapies are not designed to correct the underlying deficiency of leptin. Patients with LD are left with the burden of these chronic and uncontrolled metabolic abnormalities, which can be associated with premature mortality often due to acute pancreatitis, renal failure, severe cardiac disease, or liver failure. Therefore, there is a significant unmet medical need for a therapy that improves the metabolic disorders found in these patients.
About the AstraZeneca / Bristol-Myers Squibb Diabetes Alliance
Dedicated to addressing the global burden of diabetes by advancing individualized patient care, AstraZeneca and Bristol-Myers Squibb are working in collaboration to develop and commercialize a versatile portfolio of innovative treatment options for diabetes and related metabolic disorders that aim to provide treatment effects beyond glucose control. Find out more about the Alliance and our commitment to meeting the needs of health care professionals and people with diabetes at www.astrazeneca.com or www.bms.com.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.
About Bristol-Myers Squibb
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. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that metreleptin will receive FDA approval, that the timing of any such approval will occur within the time period described in this release or that, if approved, it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2012, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.