Back to Search
Start Over
Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naïve and alglucosidase alfa-treated patients with late-onset Pompe disease: A phase 1, open-label, multicenter, multinational, ascending dose study.
- Source :
-
Neuromuscular disorders : NMD [Neuromuscul Disord] 2019 Mar; Vol. 29 (3), pp. 167-186. Date of Electronic Publication: 2018 Dec 17. - Publication Year :
- 2019
-
Abstract
- This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths/life-threatening serious adverse events (SAEs). One Naïve patient withdrew for study drug-related SAEs (respiratory distress/chest discomfort). Infusion-associated reactions (IARs) affected 8 patients. Most treatment-emergent AEs/IARs were non-serious with mild-to-moderate intensity. At screening, 5 Switch patients tested positive for anti-avalglucosidase alfa antibodies; on-treatment, 2 Switch and 9 Naïve patients seroconverted. Post-infusion, avalglucosidase alfa plasma concentrations declined monoexponentially (t <subscript>1/2z</subscript> ∼1.0 h). AUC was 5-6 × higher in the 20 vs 5 mg/kg group. Pharmacokinetics were similar between Switch and Naïve groups and over time. Baseline quadriceps muscle glycogen was low (∼6%) in most patients, generally remaining unchanged thereafter. Exploratory efficacy parameters (pulmonary function/functional capacity) generally remained stable or improved. Avalglucosidase alfa's well-tolerated safety profile and exploratory efficacy results support further avalglucosidase alfa development.<br /> (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adult
Female
Glucan 1,4-alpha-Glucosidase pharmacology
Glycogen metabolism
Glycogen Storage Disease Type II physiopathology
Humans
Male
Middle Aged
Treatment Outcome
alpha-Glucosidases adverse effects
alpha-Glucosidases drug effects
alpha-Glucosidases pharmacokinetics
Enzyme Replacement Therapy adverse effects
Glucan 1,4-alpha-Glucosidase metabolism
Glycogen Storage Disease Type II drug therapy
alpha-Glucosidases pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2364
- Volume :
- 29
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuromuscular disorders : NMD
- Publication Type :
- Academic Journal
- Accession number :
- 30770310
- Full Text :
- https://doi.org/10.1016/j.nmd.2018.12.004