Effect of avalglucosidase alfa on disease-specific and general patient-reported outcomes in treatment-naïve adults with late-onset Pompe disease compared with alglucosidase alfa: Meaningful change analyses from the Phase 3 COMET trial

• Published in: Molecular genetics and metabolism Vol. 141; no. 2; p. 108121
• Main Authors: Toscano, Antonio, Pollissard, Laurence, Msihid, Jérôme, van der Beek, Nadine, Kishnani, Priya S., Dimachkie, Mazen M., Berger, Kenneth I., DasMahapatra, Pronabesh, Thibault, Nathan, Hamed, Alaa, Zhou, Tianyue, Haack, Kristina An, Schoser, Benedikt
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2024
• Subjects: Avalglucosidase alfa; Enzyme replacement therapy; Health-related quality of life; Late-onset Pompe disease; Meaningful change; Patient-reported outcomes; PCS; Meaningful change; FDA; ERT; PRO; Late-onset Pompe disease; mITT; SD; LOPD; Enzyme replacement therapy; HRQoL; BMI; EPOC; Health-related quality of life; OR; Avalglucosidase alfa; CI; GAA; SF-12; EQ-5D-5L; eCDF; EQ-VAS; PDSS; R-PAct; FVC; PGIC; Patient-reported outcomes; PDIS; MCS
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2023.108121

The Phase 3 COMET trial (NCT02782741) comparing avalglucosidase alfa and alglucosidase alfa included health-related quality of life (HRQoL) assessments in treatment-naïve patients with late-onset Pompe disease (LOPD). Here, we further characterize results from disease-specific and general patient-reported outcome (PRO) measures. Adults who participated in the COMET trial receiving avalglucosidase alfa or alglucosidase alfa (both 20 mg/kg biweekly) during the 49-week double-blind treatment period were included in the analysis. Proportions of patients exceeding meaningful change thresholds at Week 49 were compared post hoc between treatment groups. PROs and their meaningful change thresholds included: Pompe Disease Severity Scale (PDSS; decrease 1.0–1.5 points), Pompe Disease Impact Scale (PDIS; decrease 1.0–1.5 points), Rasch-built Pompe-specific Activity Scale (R-PAct; change from unable to able to complete activity), 12-item Short Form Health Survey (SF-12; physical component summary [PCS] score: increase ≥6 points, mental component summary [MCS] score: increase ≥7 points), EuroQol 5 Dimension 5 Level (EQ-5D-5L; improvement of ≥1 category), and Patient Global Impression of Change (PGIC; any improvement). The analysis included 99 adult patients (avalglucosidase alfa n = 50; alglucosidase alfa n = 49). Patients who received avalglucosidase alfa had significantly greater odds of achieving a meaningful change versus alglucosidase alfa for the PDSS Shortness of Breath (OR [95% CI] 11.79 [2.24; 62.18]), Fatigue/Pain (6.24 [1.20; 32.54]), Morning Headache (13.98 [1.71; 114.18]), and Overall Fatigue (5.88 [1.37; 25.11]) domains, and were significantly more likely to meet meaningful change thresholds across multiple PDSS domains (all nominal p < 0.05). A numerically greater proportion of patients in the avalglucosidase alfa group were able to complete selected activities of the R-PAct compared with the alglucosidase alfa group. Significantly greater proportions of patients who received avalglucosidase alfa achieved meaningful improvements for EQ-5D-5L usual activities dimension, EQ visual analog scale, and all four PGIC domains. The proportion of patients with improvements in SF-12 PCS and MCS was greater in the avalglucosidase alfa group versus alglucosidase alfa group, but was not significant (p > 0.05). These analyses show that avalglucosidase alfa improves multiple symptoms and aspects of daily functioning, including breathing and mobility. This supports the clinical relevance of the effects of avalglucosidase alfa on HRQoL for patients with LOPD.