NEXVIAZYME

What it is

Nexviazyme contains avalglucosidase alfa as powder for injection. Avalglucosidase alfa is a human acid α-glucosidase produced in Chinese hamster ovary cells by recombinant DNA technology, which is subsequently conjugated with approximately 7 hexamannose structures to oxidised sialic acid residues on the molecule, thereby increasing bis-M6P levels. This medicinal product is subject to additional monitoring in Australia.

Approved indications —

Patients one year of age and older with Pompe disease (acid α-glucosidase deficiency) for long-term enzyme replacement therapy.

Dosing overview

The recommended dose of Nexviazyme is 20 mg/kg of body weight administered every other week as an intravenous infusion. Dose escalation to 40 mg/kg every other week may be considered for patients with infantile onset Pompe disease (IOPD) who experience insufficient control or declining response at the lower dose. It is recommended that the infusion begins at an initial rate of 1 mg/kg/hour and is gradually increased every 30 minutes if there are no signs of infusion-associated reactions (IARs).

Key safety warnings

Hypersensitivity reactions, including anaphylaxis, have been reported in Nexviazyme treated patients. In clinical studies 86 (60.6%) patients experienced hypersensitivity reactions including 7 patients who reported severe hypersensitivity reactions and 4 patients who experienced anaphylaxis. Appropriate medical support measures, including cardiopulmonary resuscitation equipment especially for patients with cardiac hypertrophy and patients with significantly compromised respiratory function, should be readily available when Nexviazyme is administered. Infusion-associated reactions (IARs) were reported to occur at any time during and/or within a few hours after the infusion of Nexviazyme and were more likely with higher infusion rates. IARs were reported in approximately 39.4% of patients treated with Nexviazyme in clinical studies. The majority of IARs were assessed as mild to moderate and symptoms reported in more than one patient included respiratory distress, chest discomfort, dyspnoea, cough, oxygen saturation decreased, throat irritation, dyspepsia, nausea, vomiting, diarrhoea, lip swelling, erythema, palmar erythema, rash, rash erythematous, pruritus, urticaria, hyperhidrosis, skin plaque, ocular hyperemia, eyelid oedema, face oedema, increased or decreased blood pressure, tachycardia, headache, dizziness, tremor, burning sensation, pain, somnolence, sluggishness, fatigue, pyrexia, influenza like illness, chills, flushing, feeling hot or cold, cyanosis, and pallor. Treatment emergent anti-drug antibodies (ADA) were reported in both treatment naïve (95%) and treatment experienced patients (62%). In treatment-naïve patients, a trend for increases in the incidence of IARs was observed with increasing ADA titres, with the highest incidence of IARs (69.2%) reported in the high ADA peak titre range ≥12,800, compared with an incidence of 33.3% in patients with intermediate ADA titre 1,600–6,400, an incidence of 14.3% in those with low ADA titre 100–800 and an incidence of 33.3% in those who were ADA negative. Caution should be exercised when administering Nexviazyme to patients susceptible to fluid volume overload or patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function for whom fluid restriction is indicated. These patients may be at risk of serious exacerbation of their cardiac or respiratory status during infusion.

Contraindications

Life-threatening hypersensitivity to the active substance or to any of the excipients when re-challenge was unsuccessful is a contraindication.

Regulatory history

Nexviazyme (avalglucosidase alfa powder for injection 100 mg vial) was first listed on the Australian Register of Therapeutic Goods on 17 November 2021. In November 2021, the PBAC recommended not to proceed with listing on the PBS for Pompe disease.