2025/08/12 by Priya S. Kishnani, Matthias Boentert, Stephan Wenninger +8 · 1 voice
Medicine · #Child Nutrition and Feeding Issues #Glycogen Storage Diseases and Myoclonus #Lysosomal Storage Disorders Research
paper · pdf · doi:10.1002/jmd2.70033
openalex publication_date 2025/08/12 · openalex created_date 2025/08/14 · openalex updated_date 2026/07/26
ABSTRACT Pompe disease (PD) is a rare, autosomal recessive neuromuscular disorder caused by a deficiency in acid α‐glucosidase. In the Phase 3 COMET trial (NCT02782741), respiratory function was examined in participants with late‐onset PD randomized to receive enzyme replacement therapy with alglucosidase alfa (ALG; standard of care) or avalglucosidase alfa (AVA; intervention) in the primary analysis period (PAP). The open‐label extended treatment period (ETP) provided long‐term data on AVA treatment. This post hoc analysis evaluated respiratory outcomes in participants who received ALG in the PAP (Weeks 0–49) and switched to AVA in the ETP (Weeks 49–145). Participants were categorized according to improvement in upright forced vital capacity percent‐predicted (FVC) at Week 49. Forty‐four participants were included, of whom 20 (45.5%) had ΔFVC > 0% predicted at Week 49. Among ΔFVC > 0% predicted participants, FVC improved during the PAP (estimated slope [SE]: 4.0 (1.1) %/year, p < 0.01), and was maintained following switch to AVA in the ETP (0.1 (0.8) %/year, p = 0.86). For participants with ΔFVC ≤ 0% predicted during the PAP ( n = 24; estimated slope [SE]: −3.4 (1.0) %/year, p < 0.01), FVC stabilized following switch to AVA (0.3 (0.7) %/year, p = 0.70). Slopes in measures of respiratory airflow and inspiratory/expiratory muscle strength were consistent with these findings. Similar results were observed using ΔFVC ≥ 3% predicted as a measure of clinically meaningful change. This analysis demonstrates clinically meaningful maintenance in measures of lung volume (FVC) and airflow (forced expiratory volume in 1 s) after switching therapy from ALG to AVA that persists for ≥ 2 years and is independent of prior outcomes with ALG.