Galsulfase

Galsulfase Brand Name– Naglazyme

What is Galsulfase

Galsulfase is a variant of N-acetylgalactosamine 4-sulfatase, a polymorphic human enzyme.

Galsulfase, a 56kD glycoprotein, is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) cell expression system.

The recombinant protein has six asparagine-linked glycosylation sites, four of which carry a bis-mannose-6-phosphate manose7 oligosaccharide, for specific cellular recognition and uptake.

Galsulfase is used for the treatment of mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome), an autosomal recessive disorder that results from the deficiency of N-acetylgalactosamine 4-sulfatase (or arylsulfatase B) activity. N-acetylgalactosamine 4-sulfatase is necessary for the breakdown of the glycosaminoglycans (GAGs) chondroitin 4-sulfate and dermatan sulfate, and without this enzyme cells are unable to excrete the GAG residues.

Cellular accumulation of GAG residues disrupt normal cell function, and result in progressive cellular, tissue, and organ dysfunction.

Prior to the development of galsulfase, specific drug therapy to treat MPS VI has not been available, and patients only received treatment for complications related to the disorder. Enzyme replacement therapy with galsulfase has been shown to increase the catabolism of and reduce the urinary excretion of GAGs.

Three galsulfase clinical trials consisting of 54 severely debilitated MPS VI patients have been conducted.

All galsulfase treated patients demonstrated improved walking (12-minute walking test) and stair-climbing (3-minute stair climb test) capacity compared to the placebo group.

MPS VI affects approximately 1,100 individuals world wide; galsulfase has received orphan drug status for the treatment of this disorder.

Galsulfase was approved by the FDA under the brand name Naglazyme™ on June 1, 2005.

Indications

  • mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

For the treatment of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

NOTE: Galsulfase has been designated as an orphan drug for this indication by the FDA.

NOTE: When to start treatment and the optimal duration of therapy is unknown. In clinical trials, galsulfase was given to severely debilitated MPS VI patients with clinical signs and symptoms of disease

Side Effects

  1. abdominal pain
  2. anaphylactic shock
  3. anaphylactoid reactions
  4. angioedema
  5. antibody formation
  6. apnea
  7. arthralgia
  8. bradycardia
  9. bronchospasm
  10. chest pain (unspecified)
  11. chills
  12. conjunctivitis
  13. corneal opacification
  14. cough
  15. cyanosis
  16. diarrhea
  17. dyspnea
  18. erythema
  19. fever
  20. glomerulonephritis
  21. headache
  22. hearing loss
  23. hypertension
  24. hyporeflexia
  25. hypotension
  26. hypoxia
  27. infection
  28. infusion-related reactions
  29. laryngeal edema
  30. malaise
  31. nasal congestion
  32. nausea
  33. otalgia
  34. pallor
  35. paresthesias
  36. pharyngitis
  37. rash
  38. shivering
  39. sinus tachycardia
  40. spinal cord compression
  41. tachypnea
  42. thrombocytopenia
  43. urticaria
  44. vomiting

Monitoring Parameters

  • laboratory monitoring not necessary

Contraindications

  • breast-feeding
  • children
  • geriatric
  • hamster protein hypersensitivity
  • infants
  • neonates
  • pregnancy
  • respiratory infection
  • sleep apnea
  • spinal cord compression

Interactions

  • Gentamicin

Gentamicin: (Minor) There is a possible drug interaction between galsulfase and medications which may impact lysosomal efficacy.

Gentamicin slightly increases the intralysosomal pH of proximal tubular cells and decreases the activity of the lysosomal proteinases, cathepsin B and L, which are proteolytic activators of other lysosomal enzymes.

Because similar interactions have occurred between gentamicin and other therapies used for a similar disease, the effectiveness of galsulfase therapy should be monitored during coadministration.