Elosulfase Alfa (Vimzim) for the Treatment of Morquio A Syndrome (Mucopolysaccharidosis IVA, MPS IVA)

VIMIZIM (elosulfase alfa) injection, for intravenous use

Mucopolysaccharidoses comprise a group of lysosomal storage disorders caused by the deficiency of specific lysosomal enzymes required for the catabolism of glycosaminoglycans (GAG). Mucopolysaccharidosis IVA (MPS IVA, Morquio A Syndrome) is characterized by the absence or marked reduction in N-acetylgalactosamine-6-sulfatase activity. The sulfatase activity deficiency results in the accumulation of the GAG substrates, KS and C6S, in the lysosomal compartment of cells throughout the body. The accumulation leads to widespread cellular, tissue, and organ dysfunction. Vimizim is intended to provide the exogenous enzyme N-acetylgalactosamine-6-sulfatase that will be taken up into the lysosomes and increase the catabolism of the GAGs KS and C6S.


Vimizim is a formulation of elosulfase alfa, which is a purified human enzyme produced by recombinant DNA technology in a Chinese hamster ovary cell line. Human N-acetylgalactosamine-6-sulfatase (EC 3.1.6.4) is a hydrolytic lysosomal glycosaminoglycan-specific enzyme that hydrolyzes sulfate from either galactose-6-sulfate or N-acetyl-galactosamine-6-sulfate on the non-reducing ends of the glycosaminoglycans keratan sulfate (KS) and chondroitin-6-sulfate (C6S). Elosulfase alfa is a soluble glycosylated dimeric protein with two oligosaccharide chains per monomer. Each monomeric peptide chain contains 496 amino acids and has an approximate molecular mass of 55 kDa (59 kDa including the oligosaccharides). One of the oligosaccharide chains contains bis-mannose6-phosphate (bisM6P). bisM6P binds a receptor at the cell surface and the binding mediates cellular uptake of the protein to the lysosome.

Initial U.S. Approval: 2014

INDICATIONS AND USAGE
Vimizim is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome). 

DOSAGE AND ADMINISTRATION
2 mg per kg body weight administered once every week as an intravenous infusion over a minimum of 3.5 to 4.5 hours, based on infusion volume.

DOSAGE FORMS AND STRENGTHS
Injection: 5 mg/5 mL (1 mg/mL) in single-use vials. 

CONTRAINDICATIONS
None

WARNINGS AND PRECAUTIONS
Anaphylaxis and Hypersensitivity Reactions: Life-threatening anaphylaxis and hypersensitivity reactions have been observed in some patients during treatment with Vimizim. If anaphylaxis or severe hypersensitivity reactions occur, immediately stop the infusion and initiate appropriate medical treatment. Pre-treatment with antihistamines with or without antipyretics is recommended prior to the start of infusion
Risk of Acute Respiratory Complications: Patients with acute febrile or respiratory illness may be at higher risk of life-threatening complications from hypersensitivity reactions. Careful consideration should be given to the patient's clinical status prior to administration of Vimizim and consider delaying the Vimizim infusion.

ADVERSE REACTIONS
The most common adverse reactions (≥10% in Vimizim patients and occurring at a higher incidence than placebo-treated patients) were pyrexia, vomiting, headache, nausea, abdominal pain, chills, and fatigue. 

USE IN SPECIFIC POPULATIONS
Pediatric Use: The safety and effectiveness of Vimizim have not been established in pediatric patients less than 5 years of age (8.4).


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