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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

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  1. Results of an open label feasibility study of sodium valproate in people with McArdle disease

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  2. Contractile properties are impaired in congenital myopathies

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  3. MYO-MRI diagnostic protocols in genetic myopathies

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  4. BAG3 myopathy is not always associated with cardiomyopathy

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  1. Creation and implementation of a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC registry)

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  2. Phenotypic Spectrum of α-Dystroglycanopathies Associated With the c.919T>a Variant in the FKRP Gene in Humans and Mice

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  3. Bimagrumab vs Optimized Standard of Care for Treatment of Sarcopenia in Community-Dwelling Older Adults: A Randomized Clinical Trial

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  4. Vacuoles, Often Containing Glycogen, Are a Consistent Finding in Hypokalemic Periodic Paralysis

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  5. Editorial: Remaining diagnostic issues and start of a treatment era for muscle diseases

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  • Loren D M Pena
  • Richard J Barohn
  • Barry J Byrne
  • Claude Desnuelle
  • Ozlem Goker-Alpan
  • Shafeeq Ladha
  • Pascal Laforêt
  • Karl Eugen Mengel
  • Alan Pestronk
  • Jean Pouget
  • Benedikt Schoser
  • Volker Straub
  • Jaya Trivedi
  • Philip Van Damme
  • John Vissing
  • Peter Young
  • Katherine Kacena
  • Raheel Shafi
  • Beth L Thurberg
  • Kerry Culm-Merdek
  • Ans T van der Ploeg
  • NEO1 Investigator Group
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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 (t1/2z∼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.

Original languageEnglish
JournalNeuromuscular disorders : NMD
Volume29 (2019)
Pages (from-to)167-186
ISSN0960-8966
DOIs
Publication statusPublished - 1 Mar 2019

ID: 56691875