Currently Enrolling Trials
Fabrazyme is a recombinant form of human alpha-galactosidase A, which is administered intravenously to the patient in order to replace the deficient enzyme and initiate the breakdown of stored lipids.
Fabrazyme is specifically indicated for the treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease.
Fabrazyme is intended for intravenous infusion. The recommended dosage of Fabrazyme is 1 mg/kg body weight infused every two weeks as an intravenous infusion.
The initial intravenous infusion rate is 0.25 mg/min (15 mg/hour). Slow the infusion rate in the event of infusion-associated reactions.
For patients >30 kg, after patient tolerance to the infusion is well established, increase the infusion rate in increments of 0.05 to 0.08 mg/min (increments of 3 to 5 mg/hour) with each subsequent infusion. The minimum infusion duration is 1.5 hours (based on individual patient tolerability).
For patients weighing <30 kg, the maximum infusion rate is 0.25 mg/minute (15 mg/hour).
Because of the potential for severe infusion-associated reactions, appropriate medical support measures should be readily available when Fabrazyme is administered. Administer antipyretics prior to infusion of Fabrazyme.
Rechallenge: Patients who have had a positive skin test to Fabrazyme or who have tested positive for anti-Fabrazyme IgE may be successfully rechallenged with Fabrazyme. The initial rechallenge administration should be a low dose at a lower infusion rate, e.g., one-half the therapeutic dose (0.5 mg/kg) at 1/25th of the initial standard recommended rate (0.01 mg/min). Once a patient tolerates the infusion, the dose may be increased to reach the approved dose of 1 mg/kg and the infusion rate may be increased by slowly titrating upwards (doubled every 30 minutes up to a maximum rate of 0.25 mg/minute), as tolerated.
Mechanism of Action
Fabrazyme is recombinant human á-galactosidase A enzyme with the same amino acid sequence as the native enzyme. Purified agalsidase beta is a homodimeric glycoprotein. It is produced by recombinant DNA technology in a Chinese Hamster Ovary mammalian cell expression
Fabrazyme is intended to provide an exogenous source of a-galactosidase A in Fabry disease subjects. Preclinical and clinical studies evaluating a limited number of cell types indicated that Fabrazyme would catalyze the hydrolysis of glycosphingolipids including GL-3.
Adverse events associated with the use of Fabrazyme may include (but are not limited to) the following:
- Skeletal pain
FDA approval of Fabrazyme was based on a randomized, double-blind, placebo-controlled, multinational, multicenter study of 58 Fabry subjects, ages 16 to 61 years, all naïve to enzyme replacement therapy. The primary efficacy endpoint of GL-3 inclusions in renal interstitial capillary endothelial cells, was assessed by light microscopy and was graded on an inclusion severity score ranging from 0 (normal or near normal) to 3 (severe inclusions).
A GL-3 inclusion score of zero was achieved in 20 of 29 (69%) subjects treated with Fabrazyme compared to zero of 29 treated with placebo.
All 58 subjects in the randomized study participated in an open-label extension study of Fabrazyme at 1.0 mg/kg every two weeks indefinitely. At the end of six months of open-label treatment, most patients achieved a GL-3 inclusion score of 0 in capillary endothelium. GL-3 was decreased to normal or near normal levels in mesangial cells, glomerular capillary endothelium, interstitial cells and non-capillary endothelium. GL-3 deposition was still present in vascular smooth muscle cells, tubular epithelium and podocytes, at variably reduced levels. Plasma GL-3 levels were reduced to levels below the limit of detection and remained so up to 18 months of treatment.
All subjects were pretreated with acetaminophen and an antihistamine to decrease or prevent infusion associated reactions. Oral steroids were an additional option to the pretreatment regimen for patients who exhibited severe or recurrent infusion reactions.