Cytokinetics (CYTK) Reports Positive Phase IIa Data on Tirasemtiv for MG
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Cytokinetics, Incorporated (Nasdaq: CYTK) today announced positive data from a recently completed Phase IIa “Evidence of Effect” clinical trial of tirasemtiv in patients with generalized myasthenia gravis (MG). Tirasemtiv selectively activates the fast skeletal muscle troponin complex by increasing its sensitivity to calcium thereby increasing skeletal muscle force in response to neuronal input and delaying the onset and reducing the degree of muscle fatigue. Tirasemtiv, the lead drug candidate from the company’s skeletal muscle contractility program, is being evaluated as a potential treatment for amyotrophic lateral sclerosis (ALS) in BENEFIT-ALS, an international Phase IIb clinical trial that is now enrolling patients.
Phase IIa Clinical Trial in Patients with Myasthenia Gravis: Design and Results
This Phase IIa Evidence of Effect clinical trial, known as CY 4023, was a double-blind, randomized, three-period crossover, placebo-controlled, pharmacokinetic and pharmacodynamic study of tirasemtiv in patients with generalized MG. Patients enrolled in CY 4023 received single, oral, double-blind doses of placebo, 250 mg, and 500 mg of tirasemtiv in random order and approximately one week apart. The main objectives of this trial were to assess the effects of tirasemtiv on various measures of muscle strength, muscle fatigue and pulmonary function. Since CY 4023 was a hypothesis-generating trial, no single primary efficacy endpoint was pre-specified.
In CY 4023, at six hours after dosing, improvements (i.e., decreases) in the Quantitative MG score (QMG) were related to the tirasemtiv dose in a statistical significant manner (-0.49 QMG points per 250 mg; p = 0.02). The QMG is a validated index of disease severity that is often employed as a primary endpoint in clinical trials of patients with MG. In addition, decreases in certain components of the QMG and their relationships to dose were statistically significant or borderline significant. Also at six hours after dosing in CY 4023, increases in the percent predicted forced vital capacity were statistically significantly related to the dose level of tirasemtiv (2.2% per 250 mg; p = 0.04), as were the individual comparisons of each dose level of tirasemtiv versus placebo. Pending further analyses, more complete results from CY 4023 are expected to be submitted for public presentation at an upcoming clinical conference.
Both the 250 mg and 500 mg single oral doses of tirasemtiv studied in this Phase IIa clinical trial were well-tolerated by the 32 patients enrolled in CY 4023; there were no premature terminations and no serious adverse events were reported. The most commonly reported adverse event was dizziness which increased in frequency with dose and was reported as mild in all but one case that was classified as moderate.
“This study provides clear evidence of a pharmacodynamic effect of tirasemtiv to increase skeletal muscle performance and reduce fatigue in patients with generalized myasthenia gravis,” stated Donald B. Sanders, MD, Professor, Division of Neurology and Founder of the Duke Myasthenia Gravis Clinic and Chair, Tirasemtiv in Myasthenia Gravis Study Group. “This Phase IIa clinical trial represents a rigorous evaluation of the novel mechanism of action of tirasemtiv in this disease population; these data suggest that tirasemtiv may have the potential to meaningfully improve the lives of patients with myasthenia gravis and other neuromuscular diseases.”
“We have now completed Evidence-of-Effect studies of tirasemtiv in three different diseases, all of which involve impaired muscle function. In each one, single doses of tirasemtiv appeared to be well-tolerated and produced potentially clinically meaningful pharmacodynamic effects,” stated Andrew A. Wolff, MD, FACC, Cytokinetics’ Senior Vice President of Clinical Research and Development and Chief Medical Officer. “While Cytokinetics’ current focus is the rapid completion of BENEFIT-ALS, we believe these new results in patients with MG provide further validation of the potential therapeutic utility of fast skeletal muscle troponin activators across a broad spectrum of diseases characterized by muscle weakness or fatigue.”
Cytokinetics has been awarded $3.5 million in grants (Award Number RC3NS070670) from the National Institute of Neurological Disorders and Stroke (NINDS) to fund research and development of tirasemtiv in MG. Through September 30, 2012, Cytokinetics has incurred $4.1 million in research and development expense associated with its MG program, and has received $2.9 million or 69% of the program’s funding from the NINDS. The content of this press release is solely the responsibility of Cytokinetics and does not necessarily represent the official views of the NINDS or the National Institutes of Health.
Phase IIa Clinical Trial in Patients with Myasthenia Gravis: Design and Results
This Phase IIa Evidence of Effect clinical trial, known as CY 4023, was a double-blind, randomized, three-period crossover, placebo-controlled, pharmacokinetic and pharmacodynamic study of tirasemtiv in patients with generalized MG. Patients enrolled in CY 4023 received single, oral, double-blind doses of placebo, 250 mg, and 500 mg of tirasemtiv in random order and approximately one week apart. The main objectives of this trial were to assess the effects of tirasemtiv on various measures of muscle strength, muscle fatigue and pulmonary function. Since CY 4023 was a hypothesis-generating trial, no single primary efficacy endpoint was pre-specified.
In CY 4023, at six hours after dosing, improvements (i.e., decreases) in the Quantitative MG score (QMG) were related to the tirasemtiv dose in a statistical significant manner (-0.49 QMG points per 250 mg; p = 0.02). The QMG is a validated index of disease severity that is often employed as a primary endpoint in clinical trials of patients with MG. In addition, decreases in certain components of the QMG and their relationships to dose were statistically significant or borderline significant. Also at six hours after dosing in CY 4023, increases in the percent predicted forced vital capacity were statistically significantly related to the dose level of tirasemtiv (2.2% per 250 mg; p = 0.04), as were the individual comparisons of each dose level of tirasemtiv versus placebo. Pending further analyses, more complete results from CY 4023 are expected to be submitted for public presentation at an upcoming clinical conference.
Both the 250 mg and 500 mg single oral doses of tirasemtiv studied in this Phase IIa clinical trial were well-tolerated by the 32 patients enrolled in CY 4023; there were no premature terminations and no serious adverse events were reported. The most commonly reported adverse event was dizziness which increased in frequency with dose and was reported as mild in all but one case that was classified as moderate.
“This study provides clear evidence of a pharmacodynamic effect of tirasemtiv to increase skeletal muscle performance and reduce fatigue in patients with generalized myasthenia gravis,” stated Donald B. Sanders, MD, Professor, Division of Neurology and Founder of the Duke Myasthenia Gravis Clinic and Chair, Tirasemtiv in Myasthenia Gravis Study Group. “This Phase IIa clinical trial represents a rigorous evaluation of the novel mechanism of action of tirasemtiv in this disease population; these data suggest that tirasemtiv may have the potential to meaningfully improve the lives of patients with myasthenia gravis and other neuromuscular diseases.”
“We have now completed Evidence-of-Effect studies of tirasemtiv in three different diseases, all of which involve impaired muscle function. In each one, single doses of tirasemtiv appeared to be well-tolerated and produced potentially clinically meaningful pharmacodynamic effects,” stated Andrew A. Wolff, MD, FACC, Cytokinetics’ Senior Vice President of Clinical Research and Development and Chief Medical Officer. “While Cytokinetics’ current focus is the rapid completion of BENEFIT-ALS, we believe these new results in patients with MG provide further validation of the potential therapeutic utility of fast skeletal muscle troponin activators across a broad spectrum of diseases characterized by muscle weakness or fatigue.”
Cytokinetics has been awarded $3.5 million in grants (Award Number RC3NS070670) from the National Institute of Neurological Disorders and Stroke (NINDS) to fund research and development of tirasemtiv in MG. Through September 30, 2012, Cytokinetics has incurred $4.1 million in research and development expense associated with its MG program, and has received $2.9 million or 69% of the program’s funding from the NINDS. The content of this press release is solely the responsibility of Cytokinetics and does not necessarily represent the official views of the NINDS or the National Institutes of Health.
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