[HTML][HTML] Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease

M Nicolino, B Byrne, JE Wraith, N Leslie… - Genetics in …, 2009 - nature.com
M Nicolino, B Byrne, JE Wraith, N Leslie, H Mandel, DR Freyer, GL Arnold, EK Pivnick…
Genetics in medicine, 2009nature.com
Purpose: A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase
alfa in infants and children with advanced Pompe disease. Methods: Open-label, multicenter
study of IV alglucosidase alfa treatment in 21 infants 3–43 months old (median 13 months)
with minimal acid α-glucosidase activity and abnormal left ventricular mass index by
echocardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168
weeks (median 120 weeks). Survival results were compared with an untreated reference …
Abstract
Purpose: A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease.
Methods: Open-label, multicenter study of IV alglucosidase alfa treatment in 21 infants 3–43 months old (median 13 months) with minimal acid α-glucosidase activity and abnormal left ventricular mass index by echocardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks (median 120 weeks). Survival results were compared with an untreated reference cohort.
Results: At study end, 71%(15/21) of patients were alive and 44%(7/16) of invasive-ventilator free patients remained so. Compared with the untreated reference cohort, alglucosidase alfa reduced the risk of death by 79%(P< 0.001) and the risk of invasive ventilation by 58%(P= 0.02). Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks; 62%(13/21) achieved new motor milestones. Five patients were walking independently at the end of the study and 86%(18/21) gained functional independence skills. Overall, 52%(11/21) of patients experienced infusion-associated reactions; 95%(19/20) developed IgG antibodies to recombinant human lysosomal acid α-glucosidase; no patients withdrew from the study because of safety concerns.
Conclusions: In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-free survival. Treatment also improved indices of cardiomyopathy, motor skills, and functional independence.
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