MYOZYME

What it is

MYOZYME contains alglucosidase alfa. It is supplied as powder for concentrate for solution for infusion. Each 50 mg vial contains 52.5 mg alglucosidase alfa. Following reconstitution as directed, each vial contains 10.5 mL reconstituted solution and a total extractable volume of 10 mL at 5.0 mg/mL alglucosidase alfa. MYOZYME does not contain preservatives and each vial is for single use only. MYOZYME is a purified form of the lysosomal enzyme acid alfa-glucosidase and is produced by recombinant DNA technology in a Chinese hamster ovary cell line.

Approved indications

— Long-term treatment of patients with a confirmed diagnosis of Pompe disease (acid alfa-glucosidase deficiency).

Dosing overview

The recommended dosage regimen of MYOZYME is 20 mg/kg of body weight administered once every 2 weeks as an intravenous infusion. MYOZYME should be administered at an initial infusion rate of no more than 1 mg/kg/hr, with the infusion rate able to be increased by 2 mg/kg/hr every 30 minutes, after patient tolerance to the infusion rate is established, until a maximum rate of 7 mg/kg/hr is reached.

Key safety warnings

Serious hypersensitivity reactions, including life-threatening anaphylactic reactions, have been observed during MYOZYME infusion. A small number of patients (less than 1%) in clinical trials and in the commercial setting developed anaphylactic shock and/or cardiac arrest during infusion. Reactions included bronchospasm, wheezing, respiratory arrest, respiratory distress, apnoea, stridor, dyspnoea, oxygen saturation decreased, cardiac arrest, hypotension, bradycardia, tachycardia, cyanosis, vasoconstriction, flushing, chest pain, chest discomfort, throat tightness, angioedema, pharyngeal oedema, face oedema, peripheral oedema, urticaria, and rash. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available when MYOZYME is administered because of the potential for severe infusion reactions. The majority of patients (89%) developed IgG antibodies to alglucosidase alfa, with seroconversion typically occurring within 3 months of treatment. Patients treated with higher doses of MYOZYME tended to develop a more robust antibody response and experienced more infusion-associated reactions. Negative CRIM status, indicating no endogenous enzyme is detected, is a risk factor to develop high and sustained IgG antibody titres, with higher risk in CRIM negative patients versus CRIM-positive patients and contributing to a poor outcome. Severe cutaneous and possibly immune-mediated reactions have been reported with alglucosidase alfa including ulcerative and necrotising skin lesions, with skin biopsy in one patient demonstrating deposition of anti-rhGAA antibodies in the lesion. Nephrotic syndrome was observed in a few Pompe patients treated with alglucosidase alfa who had high IgG antibody titres (≥ 102,400), with renal biopsy consistent with immune complex deposition. It is recommended to perform periodic urinalysis among patients with high IgG antibody titres. Pompe patients are at increased risk of respiratory infections due to the progressive effects of the disease on the respiratory muscles. Pompe patients treated with immunosuppressive agents may be at further increased risk of developing severe infections. Fatal and life-threatening respiratory infections have been observed in some of these patients. Cardiac arrhythmia, including ventricular fibrillation, ventricular tachycardia and bradycardia, resulting in cardiac arrest or death, have been observed in infantile-onset Pompe disease patients with cardiac hypertrophy, associated with the use of general anaesthesia for the placement of a central venous catheter. Caution should be used when administering general anaesthesia for this purpose in infantile-onset Pompe disease patients with cardiac hypertrophy.

Contraindications

MYOZYME is contraindicated in patients with hypersensitivity (anaphylactic reaction) to the active substance or to any of the excipients.

PBS listing

No source document provides PBS listing information for MYOZYME.

Regulatory history

MYOZYME (alglucosidase alfa-rch 50 mg / 10 mL powder for concentrate for solution for infusion) was first listed on the Australian Register of Therapeutic Goods on 14 March 2008.