title: Aceneuramic Acid Extended Release Administration Maintains Upper Limb Muscle Strength in a 48-week Study of Subjects with GNE Myopathy: Results from a Phase 2, Randomized, Controlled Study.
abstract: GNE Myopathy (GNEM) is a progressive adult-onset myopathy likely caused by deficiency of sialic acid (SA) biosynthesis.
  
  
  
  Evaluate the safety and efficacy of SA (delivered by aceneuramic acid extended-release [Ace-ER]) as treatment for GNEM.
  
  
  
  A Phase 2, randomized, double-blind, placebo-controlled study evaluating Ace-ER 3 g/day or 6 g/day versus placebo was conducted in GNEM subjects (n = 47). After the first 24 weeks, placebo subjects crossed over to 3 g/day or 6 g/day for 24 additional weeks (dose pre-assigned during initial randomization). Assessments included serum SA, muscle strength by dynamometry, functional assessments, clinician- and patient-reported outcomes, and safety.
  
  
  
  Dose-dependent increases in serum SA levels were observed. Supplementation with Ace-ER resulted in maintenance of muscle strength in an upper extremity composite (UEC) score at 6 g/day compared with placebo at Week 24 (LS mean difference +2.33 kg, p = 0.040), and larger in a pre-specified subgroup able to walk ≥200 m at Screening (+3.10 kg, p = 0.040). After cross-over, a combined 6 g/day group showed significantly better UEC strength than a combined 3 g/day group (+3.46 kg, p = 0.0031). A similar dose-dependent response was demonstrated within the lower extremity composite score, but was not significant (+1.06 kg, p = 0.61). The GNEM-Functional Activity Scale demonstrated a trend improvement in UE function and mobility in a combined 6 g/day group compared with a combined 3 g/day group. Patients receiving Ace-ER tablets had predominantly mild-to-moderate AEs and no serious adverse events.
  
  
  
  This is the first clinical study to provide evidence that supplementation with SA delivered by Ace-ER may stabilize muscle strength in individuals with GNEM and initiating treatment earlier in the disease course may lead to better outcomes.
authors.affiliation: Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
authors.affiliation: Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Caraco
authors.affiliation: New York University School of Medicine, New York, NY, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Lau
authors.affiliation: Washington University Medical Center, St. Louis, MO, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Pestronk
authors.affiliation: University of California Los Angeles Medical Center, Los Angeles, CA, USA.
authors.forename: Perry B
authors.initials: PB
authors.lastname: Shieh
authors.affiliation: Ultragenyx Pharmaceutical, Novato, CA, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Skrinar
authors.affiliation: Ultragenyx Pharmaceutical, Novato, CA, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Koutsoukos
authors.affiliation: Ultragenyx Pharmaceutical, Novato, CA, USA.
authors.forename: Ruhi
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Ultragenyx Pharmaceutical, Novato, CA, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Martinisi
authors.affiliation: Ultragenyx Pharmaceutical, Novato, CA, USA.
authors.forename: Emil
authors.initials: E
authors.lastname: Kakkis
mesh_terms: D000293:Adolescent; D000328:Adult; D049310:Distal Myopathies / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D055815:Young Adult
chemical_list: D019158:N-Acetylneuraminic Acid
keywords: GNE Myopathy; Sialic acid; distal myopathy with rimmed vacuoles; hereditary inclusion body myopathy; myopathy therapy