Management of Gaucher disease: enzyme replacement therapy.

Abstract Starting in 1994, 3 years after the first approval of the placental-derived enzyme replacement therapy (ERT) with alglucerase, the recombinant form imiglucerase was the introduced and became the standard of care for the visceral symptoms of Gaucher disease. For patients with non-neuronopathic (type 1) Gaucher disease, ERT is safe, with few adverse/side events, and effective in reducing hepatosplenomegaly, improving hematological parameters such as anemia and thrombocytopenia, and to a lesser degree, ameliorating lung- and bone-referred disease. Dosage differences are appreciated mainly as differences in the initial slope in achieving improvements before plateauing. Because ERT does not pass the blood-brain barrier, for patients with the acute neuronopathic form (type 2), there is no substantial change in the life-threatening neurological parameters and hence ERT is not seen as efficacious; but for patients with sub-acute neuronopathic forms (type 3), ERT for the often devastating visceral symptoms, improved quality of life, and longevity make ERT part of the standard care. Due to a world-wide reduction in imiglucerase availability mid-2009 that was not resolved quickly, patients were ERT-stopped or dose-reduced, re-invigorated the movement to provide additional therapeutic options. Early access programs of two new ERTs, then at the pre-license stage, were initiated at regulatory authorities' request for patients requiring ERT. At that point, velaglucerase alfa which has the native-enzyme sequence produced in a (proprietary) human cell line, and taliglucerase alfa, which is plant-cell-derived and produced in an inexpensive platform, were completing Phase 3 clinical trials. Velaglucerase alfa was FDA-approved in February 2010 while taliglucerase alfo was approved in May 2012. Marketing of these ERTs has also targeted the extraordinarily high cost of imiglucerase. However, with > 20 years' experience with infusible ERTs, many patients are eager to consider oral options including substrate reduction and/or pharmacological chaperone treatments taken as pills or possibly oral formulations of an ERT