Abstract Details

Title A Study to Evaluate Efficacy, Safety and Tolerability of Single Doses of Tirasemtiv in Patients with Myasthenia Gravis

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) (-)

Poster/Presentation
Number 009

Objective

Background Tirasemtiv (formerly CK-2017357) is a fast skeletal troponin activator that sensitizes the sarcomere to calcium, thus increasing muscle force following sub-maximal neuronal input and reducing fatigability. In an animal model of myasthenia gravis (MG), single doses of tirasemtiv improved muscle force and reduced fatigability in situ while increasing grip strength (Nat Med. 2012 Feb 19;18(3):452-5).

Design/Methods 32 patients with AChR-antibody positive MG and muscle weakness were recruited. In a double-blind random treatment sequence, each patient received single doses of tirasemtiv 250 mg, tirasemtiv 500 mg, and placebo; each dose was separated by at least one week. Outcome measures included the Quantitative MG Score (QMG), MG Composite (MGC) and Manual Muscle Testing, Modified MG Symptom Score, and Global Assessment by patient and investigator.

Results Six hours after dosing, improvements in the QMG were statistically significant and related to the tirasemtiv dose (-0.49 QMG points per 250 mg; p = 0.02). Also at six hours after dosing, increases in the percent predicted forced vital capacity were statistically significantly related to the dose level (2.2% per 250 mg; p = 0.04), as were the individual comparisons of each tirasemtiv dose level versus placebo. QMG score improved at least 3 points in twice as many patients after 500 mg than after placebo (p=0.098). Both doses of tirasemtiv were well-tolerated; there were no premature terminations or serious adverse events. The most commonly reported adverse event was dizziness, which was mild in all but one case, which was classified as moderate.

Conclusions The results of this study suggest that tirasemtiv may improve function in MG and will be used to support further development of tirasemtiv in neuromuscular diseases.

Authors/Disclosures
Donald B. Sanders, MD, FAAN (Duke University Medical Center)	Dr. Sanders has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Accordant Health Services. Dr. Sanders has received personal compensation in the range of $0-$499 for serving as a Consultant for Cabaletta BIO. Dr. Sanders has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kashiv Biosciences. Dr. Sanders has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Momenta Pharmaceuticals. Dr. Sanders has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen RnD. Dr. Sanders has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-aventis. Dr. Sanders has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for VielaBio. Dr. Sanders has received publishing royalties from a publication relating to health care.
Jeffrey Rosenfeld, MD, PhD, FAAN (Loma Linda University School Medicine - NEUROLOGY)	Dr. Rosenfeld has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ML Biosolutions. Dr. Rosenfeld has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for MT Pharma America. Dr. Rosenfeld has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. Dr. Rosenfeld has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Rosenfeld has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Rosenfeld has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Rosenfeld has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amylyx. Dr. Rosenfeld has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for NeuroSense. Dr. Rosenfeld has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Catalyst. Dr. Rosenfeld has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Annexion. Dr. Rosenfeld has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Anelixis. Dr. Rosenfeld has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AcuraStem. Dr. Rosenfeld has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Rosenfeld has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NeuroSense. Dr. Rosenfeld has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for MT Pharma America. Dr. Rosenfeld has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Argenx. Dr. Rosenfeld has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Strongbridge Pharma. Dr. Rosenfeld has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amylyx. The institution of Dr. Rosenfeld has received research support from MT Pharma. The institution of Dr. Rosenfeld has received research support from Alexion. The institution of Dr. Rosenfeld has received research support from Healey ALS Trial Center Mass General.
Stephanie Smith	No disclosure on file
Mazen M. Dimachkie, MD, FAAN (University of Kansas Medical Center)	Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Octapharma. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ArgenX. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Catalyst. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Takeda. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medlink. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Janssen. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TACT / Treat NMD. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cabaletta Bio. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clinical Neurological Society of America, Inc . Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ig Society, Inc. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abcuro. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amicus. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nuvig. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fortrea. The institution of Dr. Dimachkie has received research support from NIH. Dr. Dimachkie has received intellectual property interests from a discovery or technology relating to health care. Dr. Dimachkie has received intellectual property interests from a discovery or technology relating to health care. Dr. Dimachkie has received publishing royalties from a publication relating to health care.
	No disclosure on file
Fady I. Malik (Cytokinetics)	No disclosure on file

��ɫ��

��ɫ��