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