Format

Send to

Choose Destination
J Neuromuscul Dis. 2016 Mar 3;3(1):49-66.

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.

Author information

1
Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
2
New York University School of Medicine, New York, NY, USA.
3
Washington University Medical Center, St. Louis, MO, USA.
4
University of California Los Angeles Medical Center, Los Angeles, CA, USA.
5
Ultragenyx Pharmaceutical, Novato, CA, USA.

Abstract

BACKGROUND:

GNE Myopathy (GNEM) is a progressive adult-onset myopathy likely caused by deficiency of sialic acid (SA) biosynthesis.

OBJECTIVE:

Evaluate the safety and efficacy of SA (delivered by aceneuramic acid extended-release [Ace-ER]) as treatment for GNEM.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

GNE Myopathy; Sialic acid; distal myopathy with rimmed vacuoles; hereditary inclusion body myopathy; myopathy therapy

PMID:
27854209
PMCID:
PMC5271423
DOI:
10.3233/JND-159900
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for IOS Press Icon for PubMed Central
Loading ...
Support Center