2024 American Academy of Neurology Abstract Website

Shafeeq Ladha¹, Pierre Carlier², John Vissing³, Mazen Dimachkie⁴, Barry Byrne⁵, Richard Barohn⁶, Priya Kishnani⁷, Eugen Mengel⁸, Sabrina Sacconi⁹, Jaya Trivedi¹⁰, Peter Young¹¹, Kristina an Haack¹², Nicole Armstrong¹², Patrick Miossec¹², Nathan Thibault¹², Susan Sparks¹², Benedikt Schoser¹³, Jordi Diaz-Manera¹⁴
¹Department of Neurology, Gregory W. Fulton ALS and Neuromuscular Center, Barrow Neurological Institute, ²Université Paris-Saclay, CEA, DRF, Service Hospitalier Frédéric Joliot, ³Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, ⁴Department of Neurology, University of Kansas Medical Center, ⁵University of Florida, ⁶University of Missouri, ⁷Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, ⁸SphinCS GmbH, Institute of Clinical Science for LSD, ⁹Department of Clinical Neurosciences, Neuromuscular Diseases Centre, University Hospital of Nice (CHU), ¹⁰University of Texas Southwestern Medical Center, ¹¹Department of Neurology, Medical Park Bad Feilnbach, ¹²Sanofi, ¹³Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University Klinikum München, ¹⁴John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust

Objective:

To assess changes in muscle fat fraction (FF) and functional efficacy in patients with late-onset Pompe disease (LOPD) after long-term treatment with avalglucosidase alfa (AVA).

Background:

NEO1 (NCT01898364) and NEO-EXT (NCT02032524 [NEO1 extension]) studied AVA, a recombinant human acid α-glucosidase enzyme replacement therapy designed for greater cellular uptake, in adults with LOPD.

Design/Methods:

Participants were treatment-naïve (Naïve, n=10) or had received alglucosidase alfa for ≥9 months (Switch, n=14) at baseline, and received AVA (5, 10, or 20 mg/kg/every other week [qow]) for 6 months. 19 participants entered NEO-EXT receiving their NEO1 AVA dose until 2016; thereafter, all received AVA 20 mg/kg/qow. We report muscle quantitative magnetic resonance imaging (qMRI) Dixon FF changes from NEO1 baseline and exploratory efficacy data up to 8 years of follow-up (cut-off: February 16, 2023). Annualized slopes were derived from linear mixed-effects models.

Results:

Baseline mean±SD hamstring %FF was Naïve: 37.8%±26.0% (n=6); Switch: 26.6%±19.3% (n=8) and quadriceps %FF was Naïve 9.8%±3.4% (n=6); Switch 13.0%±6.9% (n=8). FF% slope estimates (95% CI) for hamstring were Naïve: 1.853/year (0.962, 2.743); Switch: 1.130/year (0.284, 1.976) and for quadriceps were Naïve: 0.782/year (0.371, 1.193); Switch: 0.702/year (0.192, 1.212). These 8-year qMRI data continue the trend previously reported at 5 years. Slope estimates (95%CI) for forced vital capacity % predicted were Naïve: −0.392/year (−0.863, 0.079); Switch: −0.464/year (−0.880, −0.049) and for 6-minute walk test % predicted were Naïve: −1.165/year (−1.720, −0.611); Switch: −0.265/year (−0.719, 0.190). Compared to previously reported 6-year data, participants appear as clinically stable at 8 years.

Conclusions:

These NEO-EXT results support the clinical utility of monitoring qMRI in LOPD patients, which may be a useful biomarker of early disease progression. qMRI evidenced a trend for stabilization in most participants, supporting the observed clinical stability during 8 years of follow-up. [On behalf of NEO-EXT Investigators] Funding: Sanofi.