The safety and efficacy of alglucosidase alfa were assessed in 57 treatment-naive infantile-onset Pompe disease patients, aged 0.2 month to 3.5 years at first infusion, in three separate clinical trials.

Study 1 was an international, multicenter, open-label, clinical trial of 18 infantile-onset Pompe disease patients. This study was conducted between 2003 and 2005. Patients were randomized 1:1 to receive either 20 mg/kg or 40 mg/kg alglucosidase alfa every two weeks, with length of treatment ranging from 52 to 106 weeks. Enrollment was restricted to patients 7 months of age or younger at first infusion with clinical signs of Pompe disease and cardiac hypertrophy, and who did not require ventilatory support at study entry. Fourteen patients were cross reactive immunologic material (CRIM) positive and 4 patients were CRIM negative.

Efficacy was assessed by comparing the proportions of alglucosidase alfa-treated patients who died or needed invasive ventilator support at 18 months of age with the mortality experience of a historical cohort of untreated infantile-onset Pompe disease patients with similar age and disease severity. In the historical cohort, 61 untreated patients with infantile-onset Pompe disease diagnosed by age 6 months, born between 1982 and 2002, were identified by a retrospective review of medical charts. By 18 months of age, 15 of 18 (83%) alglucosidase alfa-treated patients were alive without invasive ventilatory support and 3 (17%) required invasive ventilator support, whereas only one of the 61 (2%) historical control patients was alive. No differences in outcome were observed between patients who received 20 mg/kg versus 40 mg/kg.

Other outcome measures in this study included unblinded assessments of motor function by the Alberta Infant Motor Scale (AIMS), a measure of infant motor performance that assesses motor maturation of the infant through age 18 months. Although gains in motor function were noted in 13 patients, the motor function was substantially delayed compared to normal infants of comparable age in the majority of patients. Two of 9 patients who had initially demonstrated gains in motor function after 12 months of alglucosidase alfa treatment regressed despite continued treatment.

Changes from baseline to Month 12 in left ventricular mass index (LVMI), a measure of pharmacodynamic effect, were evaluated by echocardiography. Fifteen patients who underwent both baseline and Month 12 echocardiograms demonstrated decreases from baseline in LVMI (mean decrease 118 g/m2, range 45 to 193 g/m2). However, the magnitude of the decrease in LVMI did not correlate with the clinical outcome measure of ventilator-free survival.

Study 2 was an international, multicenter, non-randomized, open-label clinical trial that enrolled 21 infantile-onset patients aged 3 months to 3.5 years at first infusion. Eighteen patients were CRIM positive and 3 patients were CRIM negative. All patients received 20 mg/kg alglucosidase alfa every other week for up to 104 weeks. Five of 21 patients were receiving invasive ventilatory support at the time of first infusion.

The primary outcome measure was the proportion of patients alive at the conclusion of treatment. At the 52–week interim analysis, 16 of 21 patients were alive. Sixteen patients were free of invasive ventilatory support at the time of first infusion; of these, 4 died, 2 required invasive ventilatory support, and 10 were free of invasive ventilatory support after 52 weeks of treatment. For the 5 patients who were receiving invasive ventilatory support at baseline, 1 died, and 4 remained on invasive ventilatory support at Week 52.

Study 3 was an open-label, single-center trial in 18 infantile-onset Pompe disease patients who had a confirmed diagnosis of Pompe disease as identified through a newborn screening program. All patients were CRIM positive. Patients were treated with alglucosidase alfa prior to 6 months of age (0.2 to 5.8 months at first infusion). Sixteen patients reached 18 months of age at the time of analysis, and all (100%) were alive without invasive ventilator support.