Journal article
Safety and efficacy of N-acetylmannosamine (ManNAc) in patients with GNE myopathy: an open-label phase 2 study
Genetics in medicine, Vol.23(11), pp.2067-2075
11/2021
DOI: 10.1038/s41436-021-01259-x
PMCID: PMC8553608
PMID: 34257421
Abstract
Purpose: To evaluate the safety and efficacy of N-acetylmannosamine (ManNAc) in GNE myopathy, a genetic muscle disease caused by deficiency of the rate-limiting enzyme in N-acetylneuraminic acid (Neu5Ac) biosynthesis.
Methods: We conducted an open-label, phase 2, single-center (NIH, USA) study to evaluate oral ManNAc in 12 patients with GNE myopathy (ClinicalTrials.gov NCT02346461). Primary endpoints were safety and biochemical efficacy as determined by change in plasma Neu5Ac and sarcolemmal sialylation. Clinical efficacy was evaluated using secondary outcome measures as part of study extensions, and a disease progression model (GNE-DPM) was tested as an efficacy analysis method.
Results: Most drug-related adverse events were gastrointestinal, and there were no serious adverse events. Increased plasma Neu5Ac (+2,159 nmol/L, p < 0.0001) and sarcolemmal sialylation (p = 0.0090) were observed at day 90 compared to baseline. A slower rate of decline was observed for upper extremity strength (p = 0.0139), lower extremity strength (p = 0.0006), and the Adult Myopathy Assessment Tool (p = 0.0453), compared to natural history. Decreased disease progression was estimated at 12 (γ = 0.61 [95% CI: 0.09, 1.27]) and 18 months (γ = 0.55 [95% CI: 0.12, 1.02]) using the GNE-DPM.
Conclusion: ManNAc showed long-term safety, biochemical efficacy consistent with the intended mechanism of action, and preliminary evidence clinical efficacy in patients with GNE myopathy.
Details
- Title: Subtitle
- Safety and efficacy of N-acetylmannosamine (ManNAc) in patients with GNE myopathy: an open-label phase 2 study
- Creators
- Nuria CarrilloMay C MalicdanPetcharat LeoyklangJoseph A ShraderGalen JoeChristina SlotaJohn PerreaultJohn D HeissBradley ClassChia-Ying LiuKennan BradleyColleen JodarskiCarla CicconeClaire DriscollRebecca ParksScott Van WartLevent BaymanChristopher S CoffeyMelanie QuintanaScott M BerryMarjan HuizingWilliam A Gahl
- Resource Type
- Journal article
- Publication Details
- Genetics in medicine, Vol.23(11), pp.2067-2075
- DOI
- 10.1038/s41436-021-01259-x
- PMID
- 34257421
- PMCID
- PMC8553608
- ISSN
- 1098-3600
- eISSN
- 1530-0366
- Language
- English
- Date published
- 11/2021
- Academic Unit
- Biostatistics
- Record Identifier
- 9984214663002771
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