Pharmacological Class:
Hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme.

Active Ingredient(s):
Elosulfase alfa 1mg/mL; soln for IV infusion; preservative-free.

Company
BioMarin Pharmaceuticals

Indication(s):
Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).

Pharmacology:
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 glycosaminoglycans 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.

Clinical Trials:
The safety and efficacy of Vimizim were assessed in a 24-week, randomized, double-blind, placebo-controlled clinical trial involving 176 patients with MPS IVA. The majority of the patients (82%) presented with a medical history of musculoskeletal conditions, which includes knee deformity (52%), kyphosis (31%), hip dysplasia (22%), prior spinal fusion surgery (22%) and arthralgia (20%). At baseline, all enrolled patients could walk more than 30 meters (m) but less than 325m in 6 minutes.

Patients received Vimizim 2mg/kg once per week (n=58), Vimizim 2mg/kg once every other week (n=59), or placebo (n=59). The primary endpoint was the change from baseline in the distance walked in six minutes (6-minute walk test, 6-MWT) at Week 24. The other endpoints included changes from baseline in the rate of stair climbing in three minutes (3-minute stair climb test, 3-MSCT) and changes from baseline in urine KS levels at Week 24.

The treatment effect in the distance walked in 6 minutes, compared to placebo, was 22.5m (95% CI: 4.0, 40.9; P=0.0174) in patients who received Vimizim 2mg/kg once per week. There was no difference in the rate of stair climbing between patients who received Vimizim 2mg/kg once per week and those who received placebo. Patients who received Vimizim 2mg/kg once every other week performed similarly in the 6-MWT and 3-MSCT as those who received placebo. The reduction in urinary KS levels from baseline, a measure of pharmacodynamic effect, was greater in the Vimizim treatment groups compared to placebo. The relationship between urinary KS and other measures of clinical response has not been established.

Legal Classification:
Rx

Adults & Children:
<5 years: not established. Give by IV infusion over 3.5–4.5 hours based on infusion volume. ≥5 years: 2mg/kg once weekly. Pre-treat with antihistamines with or without antipyretics 30–60 mins prior to infusion.

Warnings/Precautions:
Risk of serious anaphylactic reactions; observe patients during and after administration. Have epinephrine inj available. Discontinue immediately if severe hypersensitivity reactions occur. Acute febrile or respiratory illness; eva luate clinical status prior to therapy and consider delaying infusion. Risk of sleep apnea; consider eva luating airway patency prior to initiation. Have supplemental oxygen or continuous positive airway pressure available. Monitor for signs/symptoms of spinal or cervical cord compression. Pregnancy (Category C). Nursing mothers.

Adverse Reaction(s)
Pyrexia, vomiting, headache, nausea, abdominal pain, chills, fatigue; sleep apnea, anaphylaxis, possible antibody formation.

Notes:
To enroll in the Morquio A Registry for monitoring effects of Vimizim contact MARS@bmrn.com or call (800) 983-4587.

How Supplied:
Single-use vial (5mL)—1

LAST UPDATED:
4/3/2014