General Information

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. It is an enzyme replacement therapy, presumed to include a recombinant human form of N-acetylgalactosamine-6-sulfatase.

Vimizin is specifically indicated for Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).

Vimizin is supplied as a solution for intravenous administration. The recommended dose is 2 mg per kg given intravenously over a minimum range of 3.5 to 4.5 hours, based on infusion volume, once every week. Pre-treatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to the start of the infusion.

Clinical Results

FDA Approval
The FDA approval of Vimizin was based on a 24-week, randomized, double-blind, placebo-controlled clinical trial in 176 subjects with MPS IVA, ranging in age from 5 to 57 years. The majority of the subjects (82%) presented with a medical history of musculoskeletal conditions. At baseline, all enrolled subjects could walk more than 30 meters (m) but less than 325 m in six minutes. The subjects received Vimizin 2mg/kg every week, every other week or placebo. The primary endpoint was the change from baseline in the distance walked in six minutes (six minute walk test, 6-MWT) at Week 24. The treatment effect in the distance walked in 6 minutes, compared to placebo, was 22.5 m (CI95, 4.0, 40.9; p=0.0174) in subjects who received Vimizim 2 mg/kg once per week. There was no difference in the rate of stair climbing between treatment groups.

Mechanism of Action

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. 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. Elosulfase alfa uptake by cells into lysosomes is mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of elosulfase alfa to mannose-6-phosphate receptors.