Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease

Abstract

In a previous 52-wk trial, treatment with alglucosidase alpha markedly improved cardiomyopathy, ventilatory function, and overall survival among 18 children <7 mo old with infantile-onset Pompe disease. Sixteen of the 18 patients enrolled in an extension study, where they continued to receive alglucosidase alpha at either 20 mg/kg biweekly (n = 8) or 40 mg/kg biweekly (n = 8), for up to a total of 3 y. These children continued to exhibit the benefits of alglucosidase alpha at the age of 36 mo. Cox regression analyses showed that over the entire study period, alglucosidase alpha treatment reduced the risk of death by 95%, reduced the risk of invasive ventilation or death by 91%, and reduced the risk of any type of ventilation or death by 87%, compared with an untreated historical control group. Cardiomyopathy continued to improve and 11 patients learned and sustained substantial motor skills. No significant differences in either safety or efficacy parameters were observed between the 20 and 40 mg/kg biweekly doses. Overall, long-term alglucosidase alpha treatment markedly extended survival as well as ventilation-free survival and improved cardiomyopathy.

Figure 1

Disposition of patients in 20 mg/kg qow and 40 mg/kg qow groups.

Figure 2

Kaplan-Meier analyses of survival, survival free of invasive ventilation, and survival free of any ventilation. In each panel, thick solid lines show the Kaplan-Meier estimates for the treated patient group; thin solid lines show those for the historical control group, with 95% confidence intervals given by the corresponding dashed lines. Solid circles indicate right-censored observations. (A) Kaplan-Meier estimate of time from date of birth to death. Seven patients were right-censored from this analysis because they had not reached age 36 months by the end of the study, although they remained alive at that time. (B) Kaplan-Meier estimate of time from birth to invasive ventilator use or death. Four patients were right-censored from this analysis because they had not reached age 36 months by the end of the study, although they remained free of invasive ventilation that time. (C) Kaplan-Meier estimate of time from birth to any ventilator use or death. Four patients were right-censored from this analysis because they had not reached age 36 months by the end of the study, although they remained free of any ventilation that time. *Asterisk indicates that 1 patient from the historical control group remained alive at 36 months of age; this patient died at age 44 months.

Figure 3

Mean left ventricular mass Z-scores of treated patients from baseline to week 52; vertical bars represent standard error.