Cytokinetics Offers Update on Development Program for Tirasemtiv

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Cytokinetics, Incorporated
CYTK
provided a program update today relating to tirasemtiv, the company's lead drug candidate from its skeletal muscle contractility program.  The company announced that it has completed its review of results from BENEFIT-ALS (Blinded Evaluation of Neuromuscular Effects and Functional Improvement with Tirasemtiv in ALS) and has concluded that effects observed on Slow Vital Capacity (SVC) in patients treated with tirasemtiv are robust and potentially clinically meaningful.  In addition, following consultation with clinical and statistical experts, the company believes that data from BENEFIT-ALS support progression of tirasemtiv to a potential Phase III clinical trial in patients with amyotrophic lateral sclerosis (ALS).   The company also announced that it has begun regulatory interactions with the U.S. Food and Drug Administration (FDA) regarding results from BENEFIT-ALS and has received initial feedback from the FDA.  The company believes that effects on SVC could be a Phase III clinical trial endpoint and could support registration of tirasemtiv as a potential treatment for patients with ALS.  As a result, Cytokinetics has initiated planning for a potential Phase III clinical trial of tirasemtiv that could begin in 2015.  "We have engaged in an objective and comprehensive review of results from BENEFIT-ALS and have concluded that data favoring the effects of tirasemtiv relative to placebo on Slow Vital Capacity from this large, international Phase IIb trial are robust and warrant further investigation.  BENEFIT-ALS is the first clinical trial in patients with ALS to demonstrate a positive and potentially clinically meaningful effect on Slow Vital Capacity, an important measure of disease progression and predictor of survival," stated Robert I. Blum, Cytokinetics' President and CEO.  "We are encouraged by our initial interactions with the FDA relating to the results of BENEFIT-ALS and believe that our continuing discussions can inform our plans to pursue a potential registration program based on effects observed on respiratory function measured by Slow Vital Capacity in patients with ALS." Effects of Tirasemtiv on SVC in BENEFIT-ALS In BENEFIT-ALS, treatment with tirasemtiv resulted in a statistically significant and potentially clinically meaningful reduction in the decline of SVC, a measure of the strength of the skeletal muscles responsible for breathing that has been shown to be an important predictor of disease progression and survival in prior trials of patients with ALS. This pre-specified secondary efficacy endpoint in BENEFIT-ALS declined less on tirasemtiv than on placebo at each assessment time point. Slow Vital Capacity Placebo Tirasemtiv All (n = 210) (n = 178) (N = 388)  Baseline 89.7 (17.2) 85.7 (19.3) 87.8 (18.3)  (% Predicted, mean ± SD)  Time Point Changes from Baseline  p-value (Least Square Mean ± Standard Error)  Week 4 -3.89 (0.62) -0.99 (0.68) 0.001  Week 8 -5.81 (0.68) -2.85 (0.77) 0.004  Week 12 -8.66 (0.80) -3.12 (0.90) <0.0001   Slope of decline   (Percentage Points per day)  Week 0 to Week 12 -0.0905 -0.0394 0.0006 In addition, the reduced decline in SVC on tirasemtiv versus placebo in BENEFIT-ALS was observed consistently across all subgroups of patients.  Tirasemtiv reduced the decline in SVC versus placebo by a similar magnitude regardless of age (>65 versus <65), sex, geographic region (Europe versus North America), riluzole use, site of ALS onset (bulbar versus limb), baseline pulmonary function, baseline weight, and baseline BMI. The reduced decline in SVC versus placebo was statistically significant within each subgroup examined except patients enrolled in Europe, those with bulbar onset, and those with a percent predicted SVC less the median at baseline. Outcome measures obtained at 1 and 4 weeks after the last dose of double-blind study medication in BENEFIT-ALS also provide evidence of the durability of the effect of tirasemtiv on SVC.   Changes from Baseline Outcome Measure Baseline After 12 Weeks 1 Week after Last 4 Weeks after Last Double-Blind Double-Blind Dose Double-Blind Dose  SVC (%         predicted) Placebo  89.7 -8.66 -8.03 -10.30 Tirasemtiv  85.7 -3.12 -3.75 -5.39 p-value    <0.0001 0.0002 0.0002 Cytokinetics has performed extensive statistical analyses as well as simulations and sensitivity tests on data from BENEFIT-ALS.  In addition, the company has consulted with neuromuscular and pulmonary specialists and key opinion leaders, both in the United States and internationally, and has concluded that the results from BENEFIT-ALS provide compelling evidence that tirasemtiv may preserve respiratory function in patients with ALS that warrants investigation in a potential Phase III trial. Ongoing Regulatory Interactions and Next Steps Cytokinetics has received feedback from the FDA following initial communications regarding tirasemtiv and BENEFIT-ALS.  The company believes that the FDA may be willing to consider a potential registration path for tirasemtiv relating to effects on SVC.  The company expects to have additional interactions with the FDA and other regulatory authorities.  In addition, the company has commenced Phase III readiness activities including designing a potential Phase III clinical trial in order to inform plans, timelines and costs associated with the further development of tirasemtiv. 
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