Phase 2 Clinical Trial to Treat Rare Hereditary Muscle Disease Shows Promise

Patients with GNEM have mutations in a gene controlling a key enzyme in the synthesis pathway for sialic acid (SA). They typically experience distal muscle weakness, commonly presenting as foot drop. As the disease progresses, the muscle atrophy spreads to affect not only the lower extremities, but the upper extremities as well, leading to loss of ambulation and reliance on others for their care.

The therapy used aceneuramic acid extended release (Ace-ER) tablets in two dosages, 3 g/day and 6 g/day. For 24 weeks, one group received the 3g/day dosage, a second group received the 6g/day dosage, and a third group received a placebo. After 24 weeks, the placebo patients were switched to either the 3g/day or 6g/day dosage, while the treated groups continued at the same dosages. There were 47 patients randomized in this Phase 2 double-blind study.

Therapy with Ace-ER led to dose-dependent increases in serum sialic acid levels. Compared to placebo, patients who received the 6g/day dosages retained muscle strength in their upper extremities after 24 weeks. This effect was maintained in the upper extremities over an additional 24 weeks for the 6 g/day dose compared with the 3 g/day dose. In the lower extremities, a similar dose-dependent trend was observed but did not reach statistical significance. The maintenance of strength was also reflected in clinician- and patient-reported outcomes of the participating patients.

"In summary, this is the first evidence in humans that SA supplementation may affect the progression of muscle weakness in GNEM," explained lead investigator Zohar Argov, MD, Hadassah-Hebrew University Medical Center, Jerusalem. "This Phase 2 study included subjects at various stages of the disease including those who were advancing to a wheelchair-bound state. The findings suggest that initiating treatment earlier in the disease course may lead to better outcomes. It is our hope that the Phase 3 trial will result in the first therapeutic agent for this condition."

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NOTES FOR EDITORS

"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," by Zohar Argov, MD; Yoseph Caraco, MD; Heather Lau, MD; Alan Pestronk, MD; Perry B. Shieh, MD; Alison Skrinar, PhD; Tony Koutsoukos, PhD; Ruhi Ahmed, PhD; Julia Martinisi; and Emil Kakkis, MD, PhD (DOI 10.3233/JND-159900), published in advance of Journal of Neuromuscular Diseases, Volume 3, Issue 1 by IOS Press. The study is openly available at http://ift.tt/1TCsiOq.

Contact Daphne Watrin, IOS Press, +31 20 688 3355, d.watrin@iospress.nl for additional information. Journalists who wish to interview the authors should contact +1 844-758-7273 or ir@ultragenyx.com.  

ABOUT THE JOURNAL OF NEUROMUSCULAR DISEASES (JND)

Launched in June 2014, the Journal of Neuromuscular Diseases facilitates progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications. Guided by Editors-in-Chief Carsten G. Bönnemann (National Institute of Neurological Disorders and Stroke, NIH) and Hanns Lochmüller (Institute of Genetic Medicine, Newcastle University), the journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.

ABOUT IOS PRESS

Commencing its publishing activities in 1987, IOS Press serves the information needs of scientific and medical communities worldwide. IOS Press now (co-)publishes over 100 international journals and about 75 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.

IOS Press continues its rapid growth, embracing new technologies for the timely dissemination of information. All journals are available electronically and an e-book platform was launched in 2005. Headquartered in Amsterdam with satellite offices in the USA, Germany, India and China, IOS Press has established several strategic co-publishing initiatives. Notable acquisitions included Delft University Press in 2005 and Millpress Science Publishers in 2008.

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