FDA:s rådgivande kommitté röstar om forskningssubstansen metreleptin

Den rådgivande kommittén rekommenderar metreleptin för behandling av barn och vuxna med generaliserad lipodystrofi; rekommenderar inte för behandling av partiell lipodystrofi för den nu föreslagna indikationen

AstraZeneca och Bristol-Myers Squibb Company (BMS) meddelar idag att amerikanska FDA:s (US Food and Drug Administration) rådgivande kommitté EMDAC (Endocrinologic and Metabolic Drugs Advisory Committee) rekommenderar forskningssubstansen metreleptin för behandling av barn och vuxna med generaliserad lipodystrofi (LD). Med 11 röster mot 1 bestämde EMDAC specifikt att det finns betydande bevis för att fördelerna med metreleptin är större än riskerna vid behandling av barn och vuxna patienter med generaliserad lipodystrofi

EMDAC rekommenderade inte metreleptin till patienter med partiell LD för den nu föreslagna indikationen, med rösterna 2 mot 10. AstraZeneca och BMS vill fortfarande sträva för metreleptin som behandling av patienter med metaboliska störningar förknippade med partiell LD. Bolagen erkänner kommitténs feedback och vill fortsätta att arbeta med FDA för att identifiera lämpliga patienter med partiell LD som kan dra nytta av metreleptin.

FDA är inte bundet av EMDAC:s rekommendation men kommer att ta denna i beaktande vid översynen av BLA (Biologics License Application) för metreleptin.

LD är en grupp sällsynta syndrom som ofta förknippas med allvarliga metaboliska störningar och hög sjuklighet och dödlighet. Metreleptin granskas av FDA för behandling av barn och vuxna patienter med generaliserad lipodystrofi (LD) eller metaboliska störningar i samband med partiell LD, inklusive hypertriglyceridemi och/eller diabetes mellitus som är otillräckligt kontrollerad på aktuell behandling och/eller har tecken på leversteatos (fettlever).

Datumet för PDUFA (Prescription Drug User Fee Act) för metreleptin är satt till den 24 februari 2014. För närvarande finns det inga behandlingar som har godkänts av FDA för behandling av patienter med sällsynta former av LD (exklusive HIV-associerad LD).

EMDAC grundade sitt beslut på en genomgång av data från det kliniska utvecklingsprogrammet med metreleptin för LD. Utvecklingsprogrammet utgjorde stöd för BLA-ansökan, inklusive effekts- och säkerhetsdata från två öppna prövarsponsrade National Institutes of Health (NIH) studier, samt viktiga kompletterande effekt- och säkerhetsdata från ytterligare en öppen utökad studie på metreleptin, FHA101.

-ENDS-

 
NOTES TO EDITORS

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 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.

About Metreleptin
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 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).

About Lipodystrophy
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 “generalised,” 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 hyperglycaemia 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 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. 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.

About AstraZeneca
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. 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.

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