Title

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

Department

neurology

Document Type

Article

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 1/2z ∼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.

Medical Subject Headings

neurology

Publication Date

2019

Publication Title

Neuromuscular Disorders

ISSN

9608966

Volume

29

Issue

3

First Page

167

Last Page

186

Digital Object Identifier (DOI)

10.1016/j.nmd.2018.12.004

This document is currently not available here.

Share

COinS