Alglucosidase Alpha in Infants and Children with Pompe's Disease

Abstract

Background: Pompe’s disease is caused by a deficiency of acid alpha-glucosidase (GAA). Severe GAA deficiency manifests during infancy with rapidly progressing muscle weakness, and cardiomyopathy that typically results in death by 1 year. Aim and methods: Two open-label studies were conducted in patients 6 months (S1, n=18) or >6–36 months (S2, n=21) of age with rapidly progressing disease. S1 patients received alglucosidase alpha at 20 or 40 mg/kg qow; S2 patients started at 20 mg/kg qow. Results: Mean age at treatment and median duration of treatment were: 5.1 months and 121 weeks (S1), 15.7 months and 120 weeks (S2), respectively. Cox regression analyses comparing study patients to historical controls; (S1 n=61; S2 n=84) indicated that in patients treated at 6 months, treatment reduced risk of death by 95%, death or invasive ventilation by 91%, and death or any ventilation by 87% (all p<0.0001). In patients >6–36 months, treatment reduced risk of death by 79% (p=0.0009) and death or invasive ventilation by 58% (p=0.02). Sustained decrease in LVM occurred in 94% (S1) and 81% (S2) of patients. Normal growth occurred in >80% of patients, clinically significant motor gains in 61%. Infusion-associated reactions occurred in 56%; IgG antibodies developed in 92%. Low IgG titres or trending towards decreasing titres occurred with continued treatment in 74% of those seroconverting. Patients with two null GAA mutations and high, sustained IgG titres more often had poor long-term clinical outcomes. Conclusion: These findings demonstrate the clinical benefit of alglucosidase alfa in this population and emphasize need for early treatment.