The US FDA has approved BioMarin's Naglazyme (galsulfase) for the treatment of mucopolysaccharidosis VI (MPS VI). As the first drug approved for treatment of MPS VI, Naglazyme earns orphan drug status and 7 years of exclusivity on the market.1 Its use has been shown to increase walking and stair-climbing ability in patients diagnosed with MPS VI.2
MPS VI, a genetic disorder that occurs from a deficiency of the lysosomal enzyme N-acetylgalactosamine 4-sulfatase, affects approximately 1100 people in the world.1,3 Patients with MPS VI cannot break down certain complex carbohydrates, such as glycosaminoglycans (GAGs). As a result, the GAG substrate and carbohydrate residues collect in the cells' lysosomes, leading to dysfunction of the body's cells, tissues, and organs.3,4 Symptoms of MPS VI include deceleration of growth, liver and spleen enlargement, deformities of the joints and skeleton, and upper airway obstruction. Initial diagnosis is usually made between 6 and 24 months of age, and life expectancy for an MPS VI patient is 20 to 30 years.3
Naglazyme acts as an exogenous replacement for the enzyme that is missing in patients with MPS VI, leading to increased breakdown of GAGs and decreased lysosomal accumulation.1,4
A total of 56 patients with MPS VI participated in Naglazyme clinical trials. A randomized, double-blind, multicenter, placebo-controlled clinical trial involved 39 patients aged 5 to 29 years who were able to walk 5 to 400 meters in 12 minutes. Patients were randomized to receive either Naglazyme 1 mg/kg or placebo for 24 weeks. The Naglazyme group showed a significant increase in distance walked during 12 minutes and the rate of stair-climbing over a 3-minute period. Additionally, decreased urinary GAGs were noted in the Naglazyme group.
Following the double-blind period, an open-label study evaluated 38 patients receiving Naglazyme for 24 weeks. An increase in distance walked and stairclimbing ability was observed in both groups.
An additional 17 patients were enrolled in 2 more studies. Treatment with Naglazyme lasted for up to 144 weeks. Baseline demographics, disease progression, and urinary GAG levels were similar to the randomized trial.4
Dosing and Administration
Naglazyme is a once-a-week intravenous infusion of 1 mg/kg. Each singledose Naglazyme vial contains 5 mg; the total dose should be mixed in 0.9% sodium chloride injection, USP, and brought to a final volume of 250 mL. The dose should be infused over at least 4 hours, with an initial rate of 6 mL/h for the first hour and a maximum rate of 80 mL/h for the remaining 3 hours. If needed, the dose may be infused over up to 20 hours.
Patients weighing less than 20 kg and at risk for fluid overload may receive their dose in 100 mL of diluent; in this case, the total rate should be adjusted so that the infusion time is at least 4 hours.
Naglazyme should be administered with a polyvinyl chloride infusion set and an in-line, low-protein-binding 0.2 micrometer filter. The safety of Naglazyme in glass containers has not been studied.4
Naglazyme has been associated with an infusion reaction, which was the most common adverse reaction requiring intervention. Premedication with an antihistamine and/or antipyretics 30 to 60 minutes prior to the infusion is strongly recommended, and vital signs should be monitored throughout the infusion. The most common infusion reactions were fever, chill, rigors, headache, rash, and urticaria. Severe infusion reaction symptoms included angioneurotic edema, hypotension, bronchospasm, respiratory distress, and apnea.2 Other adverse effects included headache, fever, arthralgia, vomiting, upper respiratory infections, abdominal pain, diarrhea, ear pain, cough, and otitis media.4
Dr. Holmberg is a pharmacist with Phoenix Children's Hospital, Phoenix, Ariz.
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