NAGLAZYME

What it is

NAGLAZYME is galsulfase (rch) supplied as a 5 mg/5 mL concentrated solution for injection. NAGLAZYME is a normal variant form of the polymorphic human enzyme, N-acetylgalactosamine 4-sulfatase that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Galsulfase-rch is a lysosomal enzyme that catalyses the cleavage of the sulfate ester from terminal N-acetylgalactosamine 4-sulfate residues of glycosaminoglycans (GAG), chondroitin 4-sulfate and dermatan sulfate.

Approved indications

— NAGLAZYME is indicated as long term enzyme replacement therapy in patients with Mucopolysaccharidosis VI (MPS VI, N-acetylgalactosamine 4-sulfatase deficiency, Maroteaux-Lamy syndrome).

Dosing overview

The recommended dosage regimen of NAGLAZYME is 1 mg/kg of body weight administered once weekly as an intravenous infusion. The total volume of the infusion should be delivered over no less than 4 hours, with NAGLAZYME diluted with 0.9% Sodium Chloride Injection to a final volume of 250 mL and delivered by controlled IV infusion using an infusion pump. The initial infusion rate should be 6 mL/h for the first hour, and if the infusion is well tolerated, the rate of infusion may be increased to 80 mL/h for the remaining 3 hours. The infusion time can be extended up to 20 hours if infusion reactions occur.

Key safety warnings

Anaphylaxis and severe allergic reactions have been observed in patients during and up to 24 hours after NAGLAZYME infusion, with some reactions being life-threatening and including anaphylaxis, shock, respiratory distress, dyspnoea, bronchospasm, laryngeal oedema, and hypotension. Despite routine pretreatment with antihistamines, infusion reactions, some severe, occurred in 33 of 59 (56%) patients treated with NAGLAZYME, with serious adverse reactions during infusion including laryngeal oedema, apnoea, pyrexia, urticaria, respiratory distress, angioedema and anaphylactoid reaction. Type III immune complex-mediated reactions, including membranous glomerulonephritis have been observed with NAGLAZYME, and if immune-mediated reactions occur, discontinuation of the administration of NAGLAZYME should be considered, and appropriate medical treatment initiated. Caution should be exercised when administering NAGLAZYME to patients susceptible to fluid volume overload such as patients weighing 20 kg or less, patients with acute underlying respiratory illness, or patients with compromised cardiac and/or respiratory function, because congestive heart failure may result, and appropriate medical support and monitoring measures should be readily available during NAGLAZYME infusion. Sleep apnoea is common in MPS VI patients and antihistamine pretreatment may increase the risk of apnoeic episodes, and evaluation of airway patency should be considered prior to initiation of treatment. Spinal/cervical cord compression (SCC) with resultant myelopathy is a known and serious complication of MPS VI expected to occur in the natural history of the disease, including in patients on NAGLAZYME, and there have been post-marketing reports of patients treated with NAGLAZYME who experienced the onset or worsening of SCC requiring decompression surgery.

Contraindications

No contraindications are known.

Regulatory history

NAGLAZYME was first approved on 20 March 2007.