Kishnani Priya S, Boentert Matthias, Wenninger Stephan, Berger Kenneth I, Msihid Jérôme, O'Callaghan Lasair, Essadi-Addou Rachida, Gallego Victor, Rawat Neeraj Singh, Huynh-Ba Olivier, Diaz-Manera Jordi
Division of Medical Genetics, Department of Pediatrics Duke University Medical Center Durham North Carolina USA.
Department of Neurology Institute of Translational Neurology, Münster University Hospital Münster Germany.
JIMD Rep. 2025 Aug 12;66(5):e70033. doi: 10.1002/jmd2.70033. eCollection 2025 Sep.
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, < 0.01), and was maintained following switch to AVA in the ETP (0.1 (0.8) %/year, = 0.86). For participants with ΔFVC ≤ 0% predicted during the PAP ( = 24; estimated slope [SE]: -3.4 (1.0) %/year, < 0.01), FVC stabilized following switch to AVA (0.3 (0.7) %/year, = 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.
庞贝氏病（PD）是一种罕见的常染色体隐性神经肌肉疾病，由酸性α-葡萄糖苷酶缺乏引起。在3期COMET试验（NCT02782741）中，对晚发性PD患者的呼吸功能进行了检查，这些患者在主要分析期（PAP）被随机分配接受阿糖苷酶α（ALG；护理标准）或阿伐糖苷酶α（AVA；干预措施）的酶替代疗法。开放标签延长治疗期（ETP）提供了AVA治疗的长期数据。这项事后分析评估了在PAP（第0 - 49周）接受ALG并在ETP（第49 - 145周）改用AVA的参与者的呼吸结局。参与者根据第49周时直立用力肺活量预测百分比（FVC）的改善情况进行分类。纳入了44名参与者，其中20名（45.5%）在第49周时ΔFVC＞预测值的0%。在ΔFVC＞预测值的0%的参与者中，FVC在PAP期间有所改善（估计斜率[SE]：4.0（1.1）%/年，P＜0.01），并且在ETP改用AVA后得以维持（0.1（0.8）%/年，P = 0.86）。对于在PAP期间ΔFVC≤预测值的0%的参与者（n = 24；估计斜率[SE]： - 3.4（1.0）%/年，P＜0.01），改用AVA后FVC趋于稳定（0.3（0.7）%/年，P = 0.70）。呼吸气流和吸气/呼气肌肉力量测量指标的斜率与这些结果一致。使用ΔFVC≥预测值的3%作为具有临床意义变化的指标时，观察到了类似结果。该分析表明，从ALG转换为AVA治疗后，肺容积（FVC）和气流（1秒用力呼气量）测量指标具有临床意义的维持情况，这种情况持续≥2年，且与之前ALG治疗的结果无关。
