In the previously reported Comparative Enzyme Replacement Trial With neoGAA Versus
rhGAA (COMET) trial, avalglucosidase alfa treatment for 49 weeks showed clinically
meaningful improvements in upright forced vital capacity (FVC) percent predicted and
6-minute walk test (6MWT) compared with alglucosidase alfa.To report avalglucosidase
alfa treatment outcomes during the COMET trial extension.This phase 3 double-blind
randomized clinical trial with crossover in the extension period enrolled patients
3 years and older with previously untreated late-onset Pompe disease (LOPD) between
November 2, 2016, and February 10, 2021, with primary analysis after 49 weeks. Patients
were treated at 55 referral centers in 20 countries. Efficacy outcomes were assessed
at 97 weeks and safety outcomes to last follow-up, with data cutoff at February 10,
2021. Data were analyzed from May to June 2021.Random assignment (1:1) to receive
20 mg/kg of avalglucosidase alfa or alglucosidase alfa by intravenous infusion every
other week for 49 weeks; thereafter, all patients received 20 mg/kg of avalglucosidase
alfa every other week.The primary outcome was the least squares (LS) mean change from
baseline in FVC percent predicted. Secondary outcomes included the LS mean change
from baseline in 6MWT, muscle strength, motor function, quality of life, and disease
biomarkers. Safety and tolerability were also assessed.Of 100 participants from the
double-blind treatment period, 95 entered the extension period. Of these, 51 (54%)
were men, and the mean (range) age was 48.3 (10-79) years. At the start of this study,
mean upright FVC percent predicted was similar between treatment arms, and 6MWT distance
was greater in the avalglucosidase alfa arm. From baseline to week 97, LS mean (SE)
FVC percent predicted increased by 2.65 (1.05) for those who continued avalglucosidase
alfa and 0.36 (1.12) for those who switched to avalglucosidase alfa. The LS mean (SE)
6MWT distance increased by 18.60 (12.01) m and 4.56 (12.44) m, respectively. For participants
who switched to avalglucosidase alfa, FVC percent predicted remained stable (LS mean
[SE] change from week 49 to 97, 0.09 [0.88]) and 6MWT distance improved (LS mean [SE]
change from week 49 to 97, 5.33 [10.81] m). Potentially treatment-related adverse
events were reported in 29 patients (56.9%) who continued avalglucosidase alfa and
in 25 patients (56.8%) who switched.In this randomized clinical trial extension, maintenance
of positive clinical outcomes was demonstrated for patients continuing avalglucosidase
alfa treatment and, to a lesser extent, patients who switched from alglucosidase alfa.
No new safety concerns were observed.ClinicalTrials.gov Identifier: NCT02782741.
