Cytokinetics Offers Results from Phase IIA Trial of Tirasemtiv for Myasthenia Gravis

Cytokinetics, Incorporated(Nasdaq: CYTK) today announced positive data from a recently completed PhaseIIa "Evidence of Effect" clinical trial of tirasemtiv in patients withgeneralized myasthenia gravis (MG).  Tirasemtiv selectively activates the fastskeletal muscle troponin complex by increasing its sensitivity to calciumthereby increasing skeletal muscle force in response to neuronal input anddelaying the onset and reducing the degree of muscle fatigue. Tirasemtiv, thelead 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 nowenrolling patients.  Phase IIa Clinical Trial in Patients with Myasthenia Gravis:  Design andResultsThis Phase IIa Evidence of Effect clinical trial, known as CY 4023, was adouble-blind, randomized, three-period crossover, placebo-controlled,pharmacokinetic and pharmacodynamic study of tirasemtiv in patients withgeneralized MG.  Patients enrolled in CY 4023 received single, oral,double-blind doses of placebo, 250 mg, and 500 mg of tirasemtiv in randomorder and approximately one week apart. The main objectives of this trial wereto assess the effects of tirasemtiv on various measures of muscle strength,muscle fatigue and pulmonary function.  Since CY 4023 was ahypothesis-generating trial, no single primary efficacy endpoint waspre-specified.  In CY 4023, at six hours after dosing, improvements (i.e., decreases) in theQuantitative MG score (QMG) were related to the tirasemtiv dose in astatistical significant manner (-0.49 QMG points per 250 mg; p = 0.02).  TheQMG is a validated index of disease severity that is often employed as aprimary endpoint in clinical trials of patients with MG.  In addition,decreases in certain components of the QMG and their relationships to dosewere statistically significant or borderline significant. Also at six hoursafter dosing in CY 4023, increases in the percent predicted forced vitalcapacity were statistically significantly related to the dose level oftirasemtiv (2.2% per 250 mg; p = 0.04), as were the individual comparisons ofeach dose level of tirasemtiv versus placebo.  Pending further analyses, morecomplete results from CY 4023 are expected to be submitted for publicpresentation at an upcoming clinical conference.Both the 250 mg and 500 mg single oral doses of tirasemtiv studied in thisPhase IIa clinical trial were well-tolerated by the 32 patients enrolled in CY4023; there were no premature terminations and no serious adverse events werereported.  The most commonly reported adverse event was dizziness whichincreased in frequency with dose and was reported as mild in all but one casethat was classified as moderate.