A Randomized Study of Alglucosidase Alfa in Late-Onset Pompe's Disease

TLDR

Pompe's disease is a metabolic myopathy caused by acid alpha‑glucosidase deficiency, and late‑onset forms lead to progressive muscle weakness, respiratory decline, and early death. The study aimed to evaluate the efficacy and safety of biweekly intravenous alglucosidase alfa versus placebo in ambulatory adults with late‑onset Pompe's disease over 78 weeks. A randomized, placebo‑controlled trial enrolled 90 patients across eight centers, administering 20 mg/kg alglucosidase alfa biweekly for 78 weeks, with primary endpoints of 6‑minute walk distance and predicted forced vital capacity. At 78 weeks, alglucosidase alfa improved 6‑minute walk distance by 28.1 m and increased FVC by 3.4 percentage points (P = 0.03 and 0.006), with similar adverse event rates but some drug‑specific reactions, and overall stabilized pulmonary function over 18 months. ClinicalTrials.gov identifier NCT00158600.

Abstract

Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha glucosidase (GAA), an enzyme that degrades lysosomal glycogen. Late-onset Pompe's disease is characterized by progressive muscle weakness and loss of respiratory function, leading to early death. We conducted a randomized, placebo-controlled trial of alglucosidase alfa, a recombinant human GAA, for the treatment of late-onset Pompe's disease.Ninety patients who were 8 years of age or older, ambulatory, and free of invasive ventilation were randomly assigned to receive biweekly intravenous alglucosidase alfa (20 mg per kilogram of body weight) or placebo for 78 weeks at eight centers in the United States and Europe. The two primary end points were distance walked during a 6-minute walk test and percentage of predicted forced vital capacity (FVC).At 78 weeks, the estimated mean changes from baseline in the primary end points favored alglucosidase alfa (an increase of 28.1+/-13.1 m on the 6-minute walk test and an absolute increase of 3.4+/-1.2 percentage points in FVC; P=0.03 and P=0.006, respectively). Similar proportions of patients in the two groups had adverse events, serious adverse events, and infusion-associated reactions; events that occurred only in patients who received the active study drug included anaphylactic reactions and infusion-associated reactions of urticaria, flushing, hyperhidrosis, chest discomfort, vomiting, and increased blood pressure (each of which occurred in 5 to 8% of the patients).In this study population, treatment with alglucosidase alfa was associated with improved walking distance and stabilization of pulmonary function over an 18-month period. (ClinicalTrials.gov number, NCT00158600.)