Enzyme replacement therapy "drug holiday": results from an unexpected shortage of an orphan drug supply in Australia.

The development of recombinantly manufactured enzyme replacement therapy (ERT) has revolutionised the management of some inherited disorders of metabolism. Gaucher disease was the first lysosomal storage disorder for which ERT became commercially available and ERT remains first-line treatment for affected individuals. In Australia, 70 patients with Gaucher disease are treated through a centrally administered Australian Government national program known as the Life Savings Drug Program (LSDP). Imiglucerase (Cerezyme), manufactured by Genzyme Corporation, is the only ERT currently registered in Australia for the treatment of Gaucher disease. In June 2009, Genzyme Corporation announced the detection of a virus in its Allston Landing manufacturing facility which resulted in inventories of imiglucerase being insufficient to meet projected global demand. The Australian Government sought advice from its Gaucher Disease Advisory Committee (GDAC) on recalculating patient doses in order to ration available imiglucerase to those most in need on a clinical severity basis. Management of this rationing process was urgent and required extensive investigation to develop a clinical severity hierarchy, to review available imiglucerase stock spread across multiple pharmacies, to implement a strategy for redistributing available imiglucerase according to specific patients' recalculated doses, to advise treating doctors and patients concerning these changed circumstances and to consider new monitoring schedules during the drug shortage phase. A cohort of 24 patients was withdrawn from therapy, 22 of whom had no discernable clinical adverse effect. This experience suggests that short-term studies of maintenance therapy without a no-treatment arm may lead to erroneous conclusions and that some patients may have treatment holidays or delayed infusions without short-term adverse outcomes.