AT2101 Extension Study in Type 1 Gaucher Disease

• Research type

  Research Study

• Full title

  AN OPEN-LABEL, MULTICENTER, LONG-TERM EXTENSION STUDY TO ASSESS THE SAFETY, EFFICACY AND PHARMACODYNAMICS OF AT2101 IN ADULT PATIENTS WITH TYPE 1 GAUCHER DISEASE

• IRAS ID

  12981

• Sponsor organisation

  Amicus Therapeutics, Inc

• Eudract number

  2008-007158-36

• ISRCTN Number

  terminated

• Research summary

  Gaucher disease (GD) is a disorder caused by reduced activity of an enzyme, beta-glucocerebrosidase (GCase), that plays a key role in metabolism. The human body contains specialized cells called macrophages that remove worn-out cells by degrading them to simple molecules for recycling. This process is analogous to eating and digesting food. The macrophages "eat" worn-out cells and degrade them inside cell compartments called lysosomes that serve as the "digestive tracts" of cells. The enzyme glucocerebrosidase is located within the lysosomes and is responsible for breaking down glucocerebroside into glucose and a fat called ceramide. People with Gaucher disease lack the normal form of the glucocerebrosidase enzyme and are unable to break down glucocerebroside. Instead, the glucocerebroside remains stored within the lysosomes, preventing the macrophages from functioning normally. Enlarged macrophages containing undigested glucocerebroside are called Gaucher cells. These cells are the hallmark of this disease.Patients with Gaucher disease exhibit blood disorders such as anemia as well as skeletal impairment, and in some cases neurological impairment. The symptoms, severity, and age of onset depend in part on the genetic mutations underlying the disease.From a clinical perspective, GD has been classified into three groups: type 1, type 2 and type 3. Patients with type 1 GD, the most common subtype, display a wide range of symptoms. These symptoms include anemia, bone complications (including pathological fractures, chronic bone pain and skeletal deformities) and in a small number of patients interstitial lung disease and pulmonary hypertension.The rate of disease progression is slow in type 1, rapid in type 2, and intermediate in type 3.Current treatment options for GD include enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). These therapies have been shown to address the major blood disorders and reduce organ volume in most patients. However, neither is approved to treat the neurological symptoms or skeletal symptoms of GD.AT2101 (isofagomine [IFG] tartrate) is an iminosugar. Current data suggest that AT2101 may work by stabilizing mutant forms of GCase allowing for it to be transported to where it needs to be to perform its normal function. Studies have shown that treatment with AT2101 increases GCase total cellular enzyme levels in vitro. These results strongly support the use of AT2101 in patients with Gaucher disease.Amicus intends to develop AT2101 for the treatment of patients with type 1, 2, or 3 Gaucher disease, irrespective of treatment history, who show visceral, hematological, skeletal, and/or neurological manifestations of the disease.

• REC name

  East of England - Essex Research Ethics Committee

• REC reference

  09/H0301/6

• Date of REC Opinion

  25 Feb 2009

• REC opinion

  Further Information Favourable Opinion