Long-Term Efficacy of Alglucosidase Alfa in Late-Onset Pompe Disease (P1.120)

Objective: To examine the long-term effects of alglucosidase alfa on ambulatory function, respiratory function, and survival in LOPD patients. Background: Alglucosidase alfa has been shown to improve survival as well as respiratory and muscle function in patients with infantile-onset (IOPD) and late-onset Pompe disease (LOPD). However, there is relatively little data on long-term efficacy. Design/Methods: Data was integrated from 68 (32 F, 36 M) patients receiving up to 9 years of treatment with alglucosidase alfa during participation in 2 sequential clinical studies with alglucosidase alfa, a randomized, double blind, placebo-controlled study (LOTS, NCT00158600) and its open-label extension (NCT00455195), and in the ongoing observational Pompe Registry. Results: Mean age at symptom onset was 28.7 years (range: 2.7–53.6) and mean age at diagnosis was 34.9 years (range: 5.8–61.3). Mean age at first infusion of alglucosidase alfa was 45.8 years (range: 16–70). 71% of the 42 patients who were ventilator free at baseline remained ventilator free during follow-up. The estimated annual decline in % predicted upright forced vital capacity (FVC) prior to initiation of alglucosidase alfa was 1.3% per year, while that observed during the follow-up period was 0.78%. 53% of the 34 patients who were not using ambulatory support at baseline maintained independent ambulation during follow-up. Percent predicted 6WMD increased for the first 2–3 years after initiation of alglucosidase alfa, followed by a relatively modest decline over the next 3 years, for an absolute decrease of 6.4% over the first 6 years of treatment. 4 (5.9%) patients died during the follow-up period. Conclusions: Long-term treatment with alglucosidase alfa was associated with stabilization of respiratory and ambulatory function during the first 6 years of treatment. These data support the ability of alglucosidase alfa to slow disease progression and the long-term use of alglucosidase alfa in patients with LOPD. Study Supported by: Sanofi Genzyme Disclosure: Dr. Clemens has received personal compensation for activities with Sanofi Genzyme. Dr. Laforet has received personal compensation for activities with Sanofi Genzyme and Amicus Therapeutics for serving on a scientific advisory board. Dr. Kacena has received personal compensation for activities with Sanofi Genzyme as an employee. Dr. Sanson has received personal compensation for activities with Sanofi Genzyme as an employee. Dr. Hopkin has nothing to disclose. Dr. Van Der Ploeg has received personal compensation for activities with Sanofi Genzyme as a consultant.