Agalsidase Beta

(rINN)
Synonyms: Agalsidasum Beta; Agalsidaz Beta; Alfasidasa β.
Cyrillic synonym: Агальсидаза Бета.

💊 Chemical information

CAS — 104138-64-9 (protein moiety).
ATC — A16AB04.
ATC Vet — QA16AB04.

💊 Adverse Effects, Treatment, and Precautions

IgG antibodies to agalsidase alfa develop in some patients, and to agalsidase beta in the majority of patients. The presence of antibodies increases the risk of infusion reactions. Infusion reactions have been reported in about 14% of patients given agalsidase alfa, and in about 67% of patients treated with agalsidase beta. The frequency of the onset of these reactions decreases with continued use, with the majority of reports occurring during the first 2-4 months after the start of treatment, although onset after 1 year has also been reported. Symptoms generally start during, or within 1 hour of, infusion. The most common symptoms have included chills, dyspnoea, facial flushing, headache, nausea, fever, and fatigue. The infusion may be interrupted for about 5 to 10 minutes and restarted once symptoms have subsided. Pretreatment with oral antihistamines, paracetamol, ibuprofen, and/or corticosteroids 1 to 24 hours before infusion has been used to prevent subsequent reactions. Patients with compromised cardiac function should be monitored closely since they may be predisposed to a higher risk of severe complications arising from infusion reactions.

💊 Interactions

Agalsidase alfa or beta should not be used with amiodarone, chloroquine, monobenzone, or gentamicin, which all have the potential to inhibit intracellular
α-galactosidase activity.

💊 Pharmacokinetics

The pharmacokinetic properties of agalsidase alfa appear to be unaffected by dose; the elimination half-life from blood following a single dose has been reported to be about 100 minutes. The pharmacokinetics of agalsidase beta indicate a saturated clearance; the elimination half-life following a single dose has been reported to range from 45 to 100 minutes. However, there was no difference in pharmacodynamics between the age groups.
1. Ries M, et al. Enzyme replacement in Fabry disease: pharmacokinetics and pharmacodynamics of agalsidase alfa in children and adolescents. J Clin Pharmacol 2007; 47: 1222–30.

💊 Uses and Administration

Alpha galactosidase A is an endogenous enzyme that hydrolyses terminal α-D-galactose residues in oligosaccharides and galactolipids into more easily digestible mono- and disaccharides. A form derived from a fungal source is used to prevent intestinal gas. Agalsidase alfa and beta are recombinant forms of alpha galactosidase A used for the long-term enzyme replacement therapy of Fabry disease (see below). Agalsidase alfa is given by intravenous infusion in a dose of 200 micrograms/kg over 40 minutes, repeated every alternate week. Agalsidase beta is given by intravenous infusion in a dose of 1 mg/kg at an initial rate of no more than 250 micrograms/minute; the rate of administration may be gradually increased (by 50 to 80 micrograms/minute in each subsequent infusion) once tolerance has been established. The dose should be repeated every alternate week.

Fabry disease.

Fabry disease (Anderson-Fabry disease) is a rare X-linked recessive lysosomal storage disorder.1-6 It predominantly affects males, although female carriers may sometimes have clinical manifestations.4,5 It is characterised by a deficiency of the enzyme alpha galactosidase A resulting in the intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids, especially in vascular endothelium and smooth muscle. Symptoms include severe neuropathies, fevers, skin blemishes (angiokeratomas), corneal and lenticular opacities, and gastrointestinal disturbances. Cardiac, cerebrovascular, and renal deterioration is progressive placing patients at increased risk for early-onset myocardial infarction, stroke, and renal failure. Symptomatic treatment was the only option until the development of enzyme replacement therapy with agalsidase alfa7 and beta.8 Results from controlled studies show this form of therapy to be effective in clearing deposits from the kidneys, heart, and skin9-12 as well as improving peripheral neuropathy.13 An openlabel extension study14 of agalsidase beta in the 58 patients formerly studied in a 20-week controlled phase III study11 confirmed the continued safety and efficacy of enzyme replacement therapy after 30 months of treatment. Benefit continued in these patients followed up for a further 24 months,15 and kidney biopsies in 8 of the patients confirmed complete clearance of globotriaosylceramide. The cardiac effects of Fabry disease have been reviewed,16 and both agalsidase alfa and beta have been reported to improve left ventricular structure and function, although further studies are required. Although most studies have been in adults, enzyme replacement therapy has been shown to be safe in children over 6 years of age.17 Expert opinion generally recommends that treatment is begun as soon as clinical signs and symptoms are observed.5,18 Gene therapy19 is also under investigation.
1. Brady RO, Schiffmann R. Clinical features of and recent advances in therapy for Fabry disease. JAMA 2000; 284: 2771–5
2. Schiffmann R, Brady RO. New prospects for the treatment of lysosomal storage diseases. Drugs 2002; 62: 733–42
3. Mehta A. Agalsidase alfa: specific treatment for Fabry disease. Hosp Med 2002; 63: 347–50
4. Desnick RJ, et al. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 2003; 138: 338–46
5. Desnick RJ, et al. Fabry disease in childhood. J Pediatr 2004; 144: S20–S26
6. Clarke JTR. Narrative review: Fabry disease. Ann Intern Med 2007; 146: 425–33
7. Beck M, et al. Fabry disease: overall effects of agalsidase alfa treatment. Eur J Clin Invest 2004; 34: 838–44
8. Keating GM, Simpson D. Agalsidase beta: a review of its use in the management of Fabry disease. Drugs 2007; 67: 435–55
9. Moore DF, et al. Regional cerebral hyperperfusion and nitric oxide pathway dysregulation in Fabry disease: reversal by enzyme replacement therapy. Circulation 2001; 104: 1506–12
10. Schiffmann R, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 2001; 285: 2743–9
11. Eng CM, et al. Safety and efficacy of recombinant human αgalactosidase A replacement therapy in Fabry’s disease. N Engl J Med 2001; 345: 9–16
12. Moore DF, et al. Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement. Stroke 2002; 33: 525–31
13. Hilz MJ, et al. Enzyme replacement therapy improves function of C-, Aδ-, and Aβ-nerve fibers in Fabry neuropathy. Neurology 2004; 62: 1066–72
14. Wilcox WR, et al. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 2004; 75: 65–74
15. Germain DP, et al. Sustained, long-term renal stabilization after 54 months of agalsidase β therapy in patients with Fabry disease. J Am Soc Nephrol 2007; 18: 1547–57
16. Linhart A, Elliott PM. The heart in Anderson-Fabry disease and other lysosomal storage disorders. Heart 2007; 93: 528–35
17. Ries M, et al. Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics 2006; 118: 924–32
18. Banikazemi M, et al. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med 2007; 146: 77–86
19. Siatskas C, Medin JA. Gene therapy for Fabry disease. J Inherit Metab Dis 2001; 24 (suppl 2): 25–41.

💊 Preparations

Proprietary Preparations

Austral.: Replagal; Austria: Replagal; Belg.: Fabrazyme; Replagal; Canad.: Beano; Fabrazyme; Gaz Away; Replagal; Cz.: Fabrazyme; Replagal; Denm.: Fabrazyme; Replagal; Fin.: Fabrazyme; Fr.: Fabrazyme†; Replagal; Ger.: Fabrazyme; Replagal; Gr.: Fabrazyme; Replagal; Hung.: Fabrazyme; Replagal; Israel: Fabrazyme; Replagal; Ital.: Fabrazyme; Replagal; Jpn: Fabrazyme; Neth.: Fabrazyme; Replagal; Norw.: Fabrazyme; NZ: Fabrazyme; Replagal; Pol.: Fabrazyme; Port.: Fabrazyme; Replagal; Spain: Fabrazyme; Replagal; Swed.: Fabrazyme; Switz.: Fabrazyme; Replagal; UK: Beano; Fabrazyme; Replagal; USA: Beano; Fabrazyme.
Published November 30, 2018.