Banikazemi M et al. (2007) Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 146: 77–86

Fabry's disease results from a deficiency of the lysosomal enzyme α-galactosidase A; accumulation of this enzyme's substrates can cause renal, cardiac and cerebrovascular dysfunction, and lead to early death. In this paper, Banikazemi et al. report on a randomized, double-blind, placebo-controlled trial that investigated the effects of agalsidase beta (recombinant α-galactosidase A) on clinical outcomes in 82 adult patients with advanced Fabry's disease and mild to moderate kidney dysfunction.

The study took place from February 2001 to January 2004, and took the form of a time-to-first-event analysis of the composite end point of renal, cardiac or cerebrovascular events, or death. The FDA approved agalsidase beta in 2003 on the basis of results of studies of a surrogate marker, but required this further trial to demonstrate the drug's clinical benefit. Patients were infused with 1 mg/kg body weight agalsidase beta or placebo fortnightly for up to 35 months (mean 18.4 months). End-point events—mostly renal—were observed in 42% (13/31) of patients who received placebo, and in 27% (14/51) of the treatment group. Primary intention to treat analysis, adjusted for baseline proteinuria, revealed that agalsidase beta therapy increased the time to first clinical event compared with placebo (hazard ratio 0.47; P = 0.06).

The authors observe that patients with less-advanced Fabry's disease probably received the greatest clinical benefit from agalsidase beta. They also note that, although 61% of the treatment group and 32% of the placebo group experienced adverse events associated with the infusion therapy, only 3 of 56 serious adverse events were considered to be treatment-related.