Characterization of Response to Enzyme Replacement Therapy (ERT) in Patients With Late-Onset Pompe Disease (LOPD): A Retrospective Chart Review


Topic:

Clinical Trials

Poster Number: 55

Author(s):

Priya Kishnani MD, Mark Roberts MD, Aiesha Ahmed MD, Tarekegn Hiwot MD, Tahseen Mozaffar MD, Anthony Sileno M.S., Sheela Sitaraman , Fred Holdbrook , Zoheb Kazi , Jordi Díaz-Manera MD

Institutions:

1. Duke University Medical Center, 2. Salford Royal NHS Foundation Trust, 3. Penn State Hershey Medical Center, 4. University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Medical Center, 5. University of California Irvine, 6. Amicus Therapeutics, Inc., 7. Amicus Therapeutics, Inc., 8. Amicus Therapeutics, Inc., 9. Amicus Therapeutics, Inc., 10. Unitat de Malalties Neuromusculars, Servei de Neurologia, Hospital de la Santa Creu i Sant Pau

Background: Pompe Disease (PD) is a rare autosomal recessive disorder caused by pathogenic variants in the gene encoding acid α-glucosidase (GAA) that result in complete or partial loss of endogenous GAA activity, which is responsible for lysosomal glycogen degradation. LOPD may manifest from early childhood to adulthood and is characterized by progressive weakness, primarily in the limb-girdle and respiratory muscles, leading to motor and respiratory difficulties. Current standard of care for PD is ERT with alglucosidase alfa. Objectives: To characterize disease progression in patients with LOPD receiving ERT in a clinical setting using retrospective chart review. Results: 98 ERT-treated patients were enrolled; 44 had both a baseline (start of ERT) and ≥1 postbaseline assessment of distance walked in the 6-minute walk test (6MWT) and/or sitting forced vital capacity (FVC). The mean (SD) ages at LOPD diagnosis and enrollment were 41.3 (13.1) years and 50.6 (12.3) years, respectively. Most patients experienced motor (99%) and respiratory (78%) difficulties at enrollment. Based on available patient data at each visit, the median change from baseline in 6MWD was -15.0 meters at 0.5 years (n=9), 54.0 meters at 1.5 years (n=7), -10.0 meters at 3 years (n=9), and -15.5 meters at >3 years (n=10). Percent-predicted FVC remained stable throughout the observation period (median change: -0.5% at 3 years [n=30] and ≥3 years [n=30]). Conclusions: Although the small number of patients in the study is a limitation, findings suggest that in this cohort, ERT was associated with variable treatment response, an initial improvement in motor function during the first 2 years followed by a decline in some patients and improvement in others, and stable respiratory function, as measured by FVC. Future treatment options will address continued unmet needs in PD.