AUTHOR=Carter Chris , Boggs Tracy , Case Laura E. , Kishnani Priya 

TITLE=Real-world outcomes from a series of patients with late onset Pompe disease who switched from alglucosidase alfa to avalglucosidase alfa

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1309146

DOI=10.3389/fgene.2024.1309146

ISSN=1664-8021

ABSTRACT=<p><bold>Introduction:</bold> Pompe disease is an inherited, progressive neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase and accumulation of glycogen in tissues, resulting in cellular dysfunction, muscle damage, and functional disabilities. Enzyme replacement therapy with alglucosidase alfa (Myozyme/Lumizyme) has led to better outcomes, but many patients have plateaued or declined despite treatment. The second-generation ERT avalglucosidase alfa (Nexviazyme) was designed to have enhanced cellular uptake via the conjugation of additional bis-mannose-6-phosphate residues. There have been trials comparing the efficacy of alglucosidase and avalglucosidase, but there remains a need for more real-world data on patients who switched from alglucosidase to avalglucosidase.</p><p><bold>Methods:</bold> A chart review was conducted on <italic>n</italic> = 15 patients with late-onset Pompe disease followed at a single center who switched from alglucosidase to avalglucosidase and continued for at least 6 months.</p><p><bold>Results:</bold> A total of <italic>n</italic> = 8/15 patients received alglucosidase for more than 3 years prior to switching, and <italic>n</italic> = 7/15 received it for more than 5 years prior to switching. There were statistically significant improvements in CK, Hex4, and AST with mean differences of −104.8 U/L, −3.0 mmol/molCr, and −14.7 U/L, respectively, post-switch. 6-Minute Walk Test; comfortable gait speed; Gait, Stairs, Gower, Chair; and Quick Motor Function Test scores improved or stabilized in most patients post-switch (<italic>n</italic> = 8/12, <italic>n</italic> = 11/12, <italic>n</italic> = 9/12, <italic>n</italic> =7/11, respectively). Of <italic>n</italic> = 7 patients with pulmonary function testing, <italic>n</italic> = 4/7 had improved upright FVC. Patient-reported outcomes revealed improvements in dyspnea (<italic>n</italic> = 4/4), physical function (<italic>n</italic> = 3/4), fatigue (<italic>n</italic> = 2/3), and lower back pain (<italic>n</italic> = 3/3). Avalglucosidase was well tolerated without infusion-associated reactions, and all <italic>n</italic> = 7 patients on home infusions continued receiving ERT at home. Anti-drug antibodies were seen in <italic>n</italic> = 9/10 of patients on alglucosidase and <italic>n</italic> = 8/13 of those on avalglucosidase, with titers below 12,800 in a majority of patients. We also present the first outcome data for a patient with LOPD who is non-ambulatory and a full-time wheelchair user; she demonstrated meaningful improvements in quality of life and motor function with the switch.</p><p><bold>Discussion:</bold> In summary, improved outcomes were seen in most patients, with a subset whose decline persisted. This study presents evidence that switching from alglucosidase to avalglucosidase may be associated with improved outcomes in certain patients with LOPD.</p>