OREANDA-NEWS. January 12, 2016.   Cytokinetics, Inc. (Nasdaq:CYTK) today announced the presentation of exploratory analyses of data from EMPOWER, a Phase 3 clinical trial of dexpramipexole in patients with ALS, which demonstrated the rate of decline of slow vital capacity (SVC) predicts the risk of meaningful clinical events, including a decline in the three respiratory questions of the ALSFRS-R, as well as the time to the first occurrence of respiratory insufficiency, tracheostomy or death.  Data from placebo-treated patients in EMPOWER were provided to Cytokinetics by Knopp Biosciences.  The analyses were presented recently at the 6th Annual California ALS Research Summit in La Jolla, California.

Vital capacity measures the amount of air expelled from the lungs after a maximum inhalation and is used to assess the strength of the skeletal muscles responsible for breathing (e.g., the diaphragm). Vital capacity is often expressed in terms of the percentage of the normal value predicted for the individual patient’s sex, age, and height; i.e., percent predicted vital capacity.  It has been shown to be an important predictor of disease progression and survival in previous clinical trials in patients with ALS who typically die of respiratory failure.  Percent predicted vital capacity declines an average of 2.5-3 percentage points per month in patients with ALS and is the most frequently monitored measure of respiratory function to measure disease progression. 

To better understand the relationship of decline in SVC to the decline in other measures of respiratory function in ALS, investigators analyzed data from placebo-treated patients in EMPOWER, one of the largest clinical trials conducted in ALS. The objective of the study was to investigate the natural history of SVC decline to determine what demographic variables impact decline in SVC and how changes in SVC predict other clinically meaningful events in ALS.

Key findings from the analyses of data from EMPOWER include:

  • The overall slope of decline in percent predicted SVC from baseline through the follow-up period of 1.5 years was -0.090 percentage points per day (2.73 percentage points per month)
  • Older subjects (greater than 65) had a steeper slope of decline in SVC (-0.12 percentage points per day), as did subjects with baseline ALSFRS-R less than 39 (-0.10 percentage points per day).
  • A slowing in the decline in SVC by 0.05 percentage points per day from baseline to the month 6 visit predicted reduction in risk by 19% of any decline in the respiratory subdomain of ALSFRS-R or death; by 22% for the first onset of respiratory insufficiency or death; by 23% for first occurrence of tracheostomy or death; and by 23% for death at any time after the month 6 visit (p < 0.0001 for all).

“These findings, derived from the placebo group of a large and well-conducted clinical trial, are consistent with prior studies and suggest there is predictive value in the rate of decline of SVC for the occurrence of clinically meaningful outcomes in ALS,” said Jinsy Andrews, M.D., Cytokinetics’ Senior Director, Clinical Research and Development and Head of Neuromuscular Therapeutics.  “We look forward to the results of VITALITY-ALS which we hope may confirm and extend findings from BENEFIT-ALS as well as further explore a relationship between the decline of SVC and the time to clinically meaningful events associated with the loss of respiratory function in patients with ALS.”

About Tirasemtiv

Tirasemtiv, a novel skeletal muscle activator, 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. Tirasemtiv has been studied in clinical trials that have enrolled over 1000 people internationally.  Tirasemtiv was the subject of BENEFIT-ALS a Phase 2b, multi-national, double-blind, randomized, placebo-controlled, clinical trial which enrolled 711 patients from 73 centers in 8 countries. The primary efficacy endpoint in BENEFIT-ALS, the change from baseline to the average of the ALSFRS-R total scores obtained after 8 and 12 weeks of double-blind treatment, was not statistically different between patients treated with tirasemtiv or placebo.  Treatment with tirasemtiv in BENEFIT-ALS did result in a statistically significant and potentially clinically meaningful slowing of the rate of decline of SVC versus placebo; in addition, the reduction from baseline in SVC was statistically significantly smaller on tirasemtiv versus placebo at each time point it was assessed.  The difference in the reduction from baseline in SVC in patients treated with tirasemtiv versus those on placebo persisted for at least four weeks following the last dose of double-blind study medication.  Tirasemtiv is the subject of VITALITY-ALS, an ongoing Phase 3 clinical trial designed to confirm and extend findings from prior clinical trials.

About Cytokinetics

Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators as potential treatments for debilitating diseases in which muscle performance is compromised and/or declining. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to increase muscle function and contractility. Cytokinetics’ lead drug candidate is tirasemtiv, a fast skeletal muscle troponin activator, for the potential treatment of ALS. Tirasemtiv has been granted orphan drug designation and fast track status by the U.S. Food and Drug Administration and orphan medicinal product designation by the European Medicines Agency for the potential treatment of ALS. Cytokinetics retains the right to develop and commercialize tirasemtiv. Cytokinetics is collaborating with Amgen Inc. to develop omecamtiv mecarbil, a novel cardiac muscle activator, for the potential treatment of heart failure. Cytokinetics is collaborating with Astellas Pharma Inc. to develop CK-2127107, a fast skeletal muscle activator, for the potential treatment of spinal muscular atrophy. Amgen holds an exclusive license worldwide to develop and commercialize omecamtiv mecarbil and Astellas holds an exclusive license worldwide to develop and commercialize CK-2127107. Both licenses are subject to Cytokinetics' specified development and commercialization participation rights. For additional information about Cytokinetics, visit http://www.cytokinetics.com/.