ARM210 Granted Orphan Drug Designation for RYR1-RM Treatment


Also known as S48168, it was previously granted Orphan Drug designation as well as a Rare Pediatric Disease designation in 2015 for Duchenne Muscular Dystrophy.

US Food and Drug Administration

The FDA has granted an Orphan Drug designation to ARM210, for its potential as a treatment for patients with Ryanodine Receptor Type 1 Related Myopathies (RYR1-RM).

The ARMGO Pharma product, also known as S48168, was previously granted Orphan Drug designation as well as a Rare Pediatric Disease designation in 2015 for Duchenne Muscular Dystrophy (DMD).

"This designation represents an important achievement for the Rycal ARM210 program and highlights the unmet need to provide effective treatment for patients with RYR1-RM," said Gene Marcantonio, MD, PhD, the president and chief medical officer of ARMGO Pharma, in a statement.1 "We are looking forward to continuing the progress of the ARM210 clinical program, including upcoming studies in RYR1-RM patients."

ARM210 is a small molecule which binds to the RyR channels that are leaking and repairs them. It has demonstrated this mechanism of action in vitro in muscle biopsies from patients with RYR1-RM. The leaky channels impair muscle contraction, which in turn leads to muscle weakness and function loss, as well as the activation of toxic pathways that damage the muscle and cause symptoms of RYR1-RM.

The therapy is part of the Rycals drug class, initially discovered by Andrew R. Marks Andrew R. Marks, MD, the Clyde and Helen Wu Professor of Molecular Cardiology, chairman of the Department of Physiology and Cellular Biophysics, and founding director of the Clyde and Helen Wu Center for Molecular Cardiology at Columbia University Medical Center.

In animal models of DMD, ARM210 has revealed significant improvements in exercise capacity, muscle-specific force, grip strength, and muscle histology compared to vehicle-treated controls. In January, data from a proof-of-concept trial of the therapy as a disease modifier in dystrophin-deficient mdx mice, these improvements were seen after 4 and 12 weeks, with additional increases in cellular biomarkers of calcium homeostasis.2 In that trial, the mdx mice were treated with ARM210 at 2 concentrations of either 50 mg/kg per day or 10 mg/kg per day in their drinking water for 4 and 12 weeks, respectively.

Assessments were made via treadmill sessions twice per week (12 m/min for 30 min) to unmask the mild disease. That was followed by in vivo forelimb and hindlimb grip strength and fatigability measurements, ex vivo extensor digitorum longus (EDL) and diaphragm (DIA) force contraction measurement and histologic and biochemical analysis.


1. ARMGO Pharma Receives FDA Orphan Drug Designation for ARM210/S48168 for the Treatment of Ryanodine Receptor Type 1 Related Myopathies [press release]. Ardsley, NY: ARMGO Pharma Inc; Published September 5, 2018. Accessed September 5, 2018.

2. Capogrosso RF, Mantuano P, Uaesoontrachoon K, et al. Ryanodine channel complex stabilizer compound S48168/ARM210 as a disease modifier in dystrophin-deficient


mice: proof-of-concept study and independent validation of efficacy. Faseb J. 2018;32(2):1025-1043.


: 10.1096/fj.201700182RRR.

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