vials containing 50 mg powder for reconstitution
Approved indication: Pompe disease
Australian Medicines Handbook Appendix A
Pompe disease is a rare inherited glycogen storage disease caused by a deficiency in the enzyme acid alglucosidase alfa, which breaks down glycogen to glucose. In patients who lack this enzyme, glycogen builds up in various tissues, particularly cardiac and skeletal muscle, leading to cardiomyopathy, progressive muscle weakness and impaired respiratory function. Early-onset disease typically leads to death from cardiorespiratory failure within the first year of life.
This recombinant form of human alglucosidase alfa is produced in Chinese hamster ovary cells. The recommended dose is 20 mg/kg given as an intravenous infusion every two weeks. Its elimination half-life is 2-3 hours.
The efficacy of recombinant alglucosidase alfa (20 mg/kg or 40 mg/kg fortnightly) has been assessed in 18 infants with Pompe disease (aged 7 months or younger), and compared to a historical cohort of 61 untreated infants. All patients given alglucosidase alfa survived until 18 months of age compared with only one of the 61 untreated controls. However, three of the treated infants required invasive ventilatory support during the study. Thirteen of the 18 treated infants had improved motor development by week 52 of treatment with seven of them being able to walk independently. In general, the higher alglucosidase alfa dose (40 mg/kg) did not seem to offer any clear advantage over the lower dose (20 mg/kg).1
In a similarly designed trial, 21 infants aged 3-36 months were given alglucosidase alfa 20 mg/kg fortnightly. Of the 16 infants who did not need invasive ventilatory support at enrolment, four had died, two required invasive ventilatory support and ten did not after a year of treatment. Of the five infants who needed ventilatory support at baseline, one had died and four still required ventilation. A historical comparison of the treated infants with 86 untreated infants showed no significant difference in mortality rate. The trial was inconclusive probably due to the heterogeneous study population.
Around half of the children treated with alglucosidase alfa had an infusion-related reaction, which included fever, rash, urticaria, cough, decreased oxygen saturation, vomiting, flushing and tachycardia. These were usually managed by slowing or interrupting the infusion or giving an antipyretic, antihistamine or corticosteriod. Life-threatening anaphylactic reactions have been reported. Pneumonia, respiratory failure or distress, intravenous catheter-related infection, respiratory syncytial virus infection and gastroenteritis have also occurred following treatment.1
There is an increased risk of cardiac arrhythmia and sudden death during general anaesthesia for central venous catheter replacement. This has been observed in patients with cardiac hypertrophy. Acute respiratory failure has also occurred in one infant following an infusion of alglucosidase alfa. This was possibly associated with fluid overload.
Most infants developed antibodies to the recombinant alglucosidase alfa within three months of starting treatment. High antibody titres have been associated with reduced efficacy and increased incidence of infusion reactions.1
Alglucosidase alfa replacement therapy is the only treatment available for improving the short-term survival of infants with Pompe disease. The long-term prognosis of these patients is not known. As there is a potential for serious adverse events, appropriate medical support, including resuscitation equipment, should be available when treating patients. The effectiveness of alglucosidase alfa in late-onset Pompe disease has not so far been established.
The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
- Kishnani PS, Corzo D, Nicolino M, Byrne B, Mandel H. Recombinant human acid Î±-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology 2007;68:99-109. .