Abstract
BACKGROUND AND OBJECTIVES: In the COMET trial, avalglucosidase alfa treatment for late-onset Pompe disease was safe, tolerable and associated with stabilization or improvement in disease parameters through 97 weeks. We report outcomes in the trial extension through 145 weeks of treatment. METHODS: In this phase 3, double-blind, randomized trial, participants with previously untreated late-onset Pompe disease were randomly assigned to receive 20 mg/kg avalglucosidase alfa or alglucosidase alfa every other week for 49 weeks; thereafter, all patients received 20 mg/kg avalglucosidase alfa every other week. For this analysis, efficacy was assessed at 145 weeks and safety to last follow-up (data cutoff: March 11, 2022). RESULTS: Of 100 participants in the double-blind treatment period, 95 entered the open-label extension, and 88 completed ≥ 145 weeks of treatment. At study start, the mean upright FVC percent predicted was similar between treatment arms, and 6MWT distance was greater in the avalglucosidase alfa arm. From baseline to week 145, the LS mean (SE) FVC percent predicted increased by 1.38 (1.22) in the avalglucosidase alfa arm and 1.25 (1.34) in the switch arm. The LS mean (SE) 6MWT distance walked increased by 20.65 (9.60) m and 0.29 (10.42) m, respectively. Potentially treatment-related adverse events were reported in 27 patients (53%) in the avalglucosidase alfa arm and 25 patients (57%) in the switch arm. Anti-drug antibodies declined over time in both arms. CONCLUSIONS: In this randomized clinical trial extension, positive clinical outcomes were maintained for patients taking avalglucosidase alfa for up to 145 weeks with no new safety concerns. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02782741, https://clinicaltrials.gov/ct2/show/NCT02782741 . Registration date: 2016-05-23; Date of first patient enrolled: 2016-11-02.