RT Journal Article
SR Electronic
T1 Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 10.1212/WNL.0000000000200746
DO 10.1212/WNL.0000000000200746
A1 Dimachkie, Mazen M
A1 Barohn, Richard J.
A1 Byrne, Barry
A1 Goker-Alpan, Ozlem
A1 Kishnani, Priya S
A1 Ladha, Shafeeq
A1 Laforêt, Pascal
A1 Mengel, Karl Eugen
A1 Peña, Loren D.M.
A1 Sacconi, Sabrina
A1 Straub, Volker
A1 Trivedi, Jaya
A1 Van Damme, Philip
A1 van der Ploeg, Ans T
A1 Vissing, John
A1 Young, Peter
A1 Haack, Kristina An
A1 Foster, Meredith
A1 Gilbert, Jane M
A1 Miossec, Patrick
A1 Vitse, Olivier
A1 Zhou, Tianyue
A1 Schoser, Benedikt
A1 ,
YR 2022
UL http://n.neurology.org/content/early/2022/05/26/WNL.0000000000200746.abstract
AB Background and Objectives: Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase (GAA) and subsequent glycogen accumulation. Avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy designed for increased cellular uptake and glycogen clearance, has been studied for long-term efficacy and safety in patients with late-onset Pompe disease (LOPD). Here we report up to 6.5 years’ experience with avalglucosidase alfa during the NEO1 and NEO-EXT studies.Methods: NEO1 participants with LOPD, either treatment-naïve (Naïve Group) or receiving alglucosidase alfa for ≥9 months (Switch Group), received avalglucosidase alfa (5, 10, or 20 mg/kg every other week [qow]) for 6 months before entering NEO-EXT and continued their NEO1 dose until all proceeded with 20 mg/kg qow. Safety and efficacy, a pre-specified exploratory secondary outcome, were assessed; slopes of change for efficacy outcomes were calculated from a repeated mixed-measures model.Results: Twenty-four participants enrolled in NEO1 (Naïve Group, n=10; Switch Group, n=14); 21 completed and 19 entered NEO-EXT; in February 2020, 17 participants remained in NEO-EXT, with data up to 6.5 years. Avalglucosidase alfa was generally well-tolerated during NEO-EXT, with a safety profile consistent with that in NEO1. No deaths or treatment-related life-threatening serious adverse events occurred. Eighteen participants developed anti-drug antibodies without apparent impact on clinical outcomes. No participants who were tested developed immunoglobulin E antibodies. Upright forced vital capacity (FVC) %predicted remained stable in most participants, with slope estimates (95% confidence intervals) of −0.473/year (−1.188, 0.242) and −0.648/year (−1.061, −0.236) in the Naïve and Switch Groups, respectively. Six-minute walk test (6MWT) %predicted was also stable for most participants, with slope estimates of −0.701/year (−1.571, 0.169) and −0.846/year (−1.567, −0.125) for the Naïve and Switch Groups, respectively. Improvements in 6MWT distance were observed in most participants aged <45 years at NEO1 enrollment, in both the Naïve and Switch Groups.Discussion: Avalglucosidase alfa was generally well-tolerated for up to 6.5 years in adult participants with LOPD either naïve to alglucosidase alfa or who had previously received alglucosidase alfa for ≥9 months.Classification of Evidence: This study provides Class IV evidence of long-term tolerability and sustained efficacy of avalglucosidase alfa in patients with LOPD after up to 6.5 years.