Agalsidase alfa

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Replagal (Orphan)

vials containing 3.5 mL concentrate

Approved indication: Fabry's disease

Australian Medicines Handbook section 10.6

Agalsidase alfa is a recombinant form of α-galactosidase A approved in Australia for Fabry's disease. It is produced using human cell lines, but the process should ensure viral safety. Like agalsidase beta, agalsidase alfa is given by infusion every two weeks, however a shorter infusion time (40 minutes) is recommended.

In a six-month trial 14 men with Fabry's disease were randomised to receive agalsidase alfa and 12 were given placebo infusions. At the end of the trial renal biopsies showed a 21% increase in the proportion of normal glomeruli in patients given agalsidase and a 27% decrease in the placebo group. Renal function, assessed by creatinine clearance, decreased in the placebo group, but not in the active treatment group. Agalsidase also significantly reduced the urinary concentration of globotriaosylceramide (the glycosphingolipid which accumulates in Fabry's disease).1

Unlike the main trial of agalsidase beta2, the effect of enzyme replacement on neuropathic pain was a major focus of the trial of agalsidase alfa. Patients given agalsidase had small, but statistically significant changes in the severity of their pain and four were able to stop taking analgesics.1

Infusion reactions are the most common adverse effects of agalsidase alfa. These reactions may not develop until patients have had a few months of treatment. More than half the patients develop antibodies to the enzyme.

There are differences between the alfa and beta forms of agalsidase, but it is difficult to compare their effectiveness as the trials1,2 had different designs.3 The US Food and Drug Administration has approved agalsidase beta, but not agalsidase alfa. Further research is needed to determine the best use of these expensive products. For example, will they change the outcomes for patients if they are started early in the course of the disease?

References

  1. Schiffmann R, Kopp JB, Austin HA, Sabnis S, Moore DF, Weibel T, et al. Enzyme replacement therapy in Fabry disease. JAMA 2001;285:2743-9.
  2. International Collaborative Fabry Disease Study Group. Safety and efficacy of recombinant human β-galactosidase A replacement therapy in Fabry's disease. N Engl J Med 2001;345:9-16.
  3. Pastores GM, Thadhani R. Enzyme-replacement therapy for Anderson-Fabry disease. Lancet 2001;358:601-3.