Cytokinetics Announces Additional Data from BENEFIT-ALS to be Presented at the 13th International Congress on Neuromuscular Diseases
Jul 3 14
Cytokinetics, Incorporated announced that additional data from BENEFIT-ALS (Blinded Evaluation of Neuromuscular Effects and Functional Improvement with Tirasemtiv in ALS) will be presented during a poster presentation scheduled at the 13th International Congress on Neuromuscular Diseases to be held July 5-10, 2014 at the Acropolis Convention Centre in Nice, France. The poster will include the first public presentation of the effects of tirasemtiv across patient subgroups on pre-specified secondary endpoints.
Cytokinetics, Incorporated Announces Additional Results from BENEFIT-ALS
Jun 2 14
Cytokinetics, Incorporated announced that additional results from BENEFIT-ALS (Blinded Evaluation of Neuromuscular Effects and Functional Improvement with Tirasemtiv in ALS) were presented during the Joint Congress of European Neurology at the International Congress Center in Istanbul, Turkey. The new data from BENEFIT-ALS were presented by Jeremy M. Shefner, M.D., Ph.D., Professor and Chair, Department of Neurology at the Upstate Medical University, State University of New York and the Lead Investigator for BENEFIT-ALS. In BENEFIT-ALS, patients with amyotrophic lateral sclerosis (ALS) were randomized 1:1 to double-blind treatment with tirasemtiv or placebo for 12 weeks. The primary outcome measure, the ALS Functional Rating Scale in its revised form (ALSFRS-R), and secondary outcomes measures of respiratory performance and other measures of skeletal muscle function and fatigability were assessed after 4, 8, and 12 weeks of double-blind treatment, and again at 1 and 4 weeks after the last dose of double-blind treatment. The results from double-blind treatment during BENEFIT-ALS were presented at the Annual Meeting of the American Academy of Neurology. Differences detected during double-blind treatment in the percentage changes from baseline in Muscle Strength Mega-Score between tirasemtiv and placebo were not sustained during the follow-up period. No differences in Maximum Voluntary Ventilation and Hand Grip Fatigue were observed on tirasemtiv versus placebo during double-blind treatment nor during the period through 4 weeks after the last double-blind dose. These data suggest that tirasemtiv may have effects on the respiratory muscles involved in performing the Slow Vital Capacity assessment that extend beyond its immediate pharmacologic action, stated Andrew A. Wolff, M.D., F.A.C.C., Cytokinetics' Chief Medical Officer and Senior Vice President of Clinical Research and Development. The absence of a difference between tirasemtiv and placebo on muscle strength and other endpoints at 4 weeks after double-blind treatment is consistent with diminishing pharmacologic effects of tirasemtiv following its discontinuation. They are encouraged by these results and are continuing its analyses of data from BENEFIT-ALS to inform the potential further development of tirasemtiv in patients with ALS. Tirasemtiv is the lead drug candidate from Cytokinetics' skeletal muscle contractility program. Tirasemtiv selectively activates the fast skeletal muscle troponin complex by increasing its sensitivity to calcium and, in preclinical studies and early clinical trials, demonstrated increases in skeletal muscle force in response to neuronal input and delays in the onset and reductions in the degree of muscle fatigue. BENEFIT-ALS was a Phase IIb, multi-national, double-blind, randomized, placebo-controlled, clinical trial designed to evaluate the safety, tolerability and efficacy of tirasemtiv in patients with amyotrophic lateral sclerosis (ALS). BENEFIT-ALS enrolled 711 patients in 73 centers in 8 countries. Patients enrolled in BENEFIT-ALS began treatment with open-label tirasemtiv at 125 mg twice daily. 605 patients were randomized 1:1 to receive 12 weeks of double-blind treatment with twice-daily oral ascending doses of tirasemtiv or placebo (302 to placebo; 303 to tirasemtiv), beginning at 125 mg twice daily and increasing weekly up to 250 mg twice daily (or a dummy dose titration with placebo). Clinical assessments occurred every four weeks during double-blind treatment; patients also returned for follow-up evaluations at one and four weeks after their final dose of double-blind study medication. The primary efficacy analysis of BENEFIT-ALS compared the mean change from baseline in the ALS Functional Rating Scale in its revised form (ALSFRS-R) to the average of the scores obtained after 8 and 12 weeks of double-blind treatment on tirasemtiv versus placebo. Secondary endpoints evaluated measures of respiratory performance and other measures of skeletal muscle function and fatigability were assessed after 4, 8, and 12 weeks of double-blind treatment (n = 210, 204, and 199 for placebo and 174, 151 and 144 for tirasemtiv, respectively), and again at 1 and 4 weeks after the last dose of double-blind treatment (n = 191 and 188 for placebo and 156 and 164 for tirasemtiv, respectively). BENEFIT-ALS did not achieve its primary efficacy endpoint (ALSFRS-R) on tirasemtiv versus placebo (-2.98 points in the tirasemtiv group versus -2.40 points in the placebo group, p = 0.11). However, treatment with tirasemtiv in BENEFIT-ALS resulted in a statistically significant and potentially clinically meaningful reduction in the decline of Percent Predicted Slow Vital Capacity (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. After 12 weeks of double-blind treatment, SVC declined by 8.66 percentage points on placebo compared to 3.12% points on tirasemtiv (p < 0.0001). The Muscle Strength Mega-Score, a measure of strength combining the data from several muscle groups in each patient, declined more slowly on tirasemtiv versus placebo (p = 0.016 for the difference in slope of decline); however, there were no differences at any time point that reached statistical significance. The rate of decline for Sniff Nasal Inspiratory Pressure (SNIP) was not statistically significant different (p = 0.21); however, SNIP decreased more on tirasemtiv compared with placebo in a statistically significant manner at 4 and 12 weeks (p values at 4, 8, and 12 weeks were 0.012, 0.066, 0.050, respectively). No differences in Maximum Voluntary Ventilation and Hand Grip Fatigue were observed on tirasemtiv versus placebo. Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that afflicts approximately 25,000 people in the United States and a comparable number of patients in Europe. Approximately 5,600 new cases of ALS are diagnosed each year in the United States. The average life expectancy of an ALS patient is approximately three to five years after diagnosis and only 10% of patients survive for more than 10 years. Death is usually due to respiratory failure because of diminished strength in the skeletal muscles responsible for breathing. Few treatment options exist for these patients, resulting in a high unmet need for new therapeutic options to address the symptoms and modify the disease progression of this grievous illness.
Cytokinetics, Incorporated Presents at Jefferies 2014 Global Healthcare Conference, Jun-04-2014 08:30 AM
May 8 14
Cytokinetics, Incorporated Presents at Jefferies 2014 Global Healthcare Conference, Jun-04-2014 08:30 AM. Venue: Grand Hyatt, New York, New York, United States. Speakers: Robert I. Blum, Chief Executive Officer, President, Director and Chief Executive of the Biopharmaceutical Concern.
Cytokinetics, Incorporated Presents at JMP Securities Healthcare Conference, Jun-24-2014 10:30 AM
May 8 14
Cytokinetics, Incorporated Presents at JMP Securities Healthcare Conference, Jun-24-2014 10:30 AM. Venue: The Westin New York Grand Central, 212 East 42nd Street, New York, NY 10017, United States.