Investigational ALS Drug Fails in Phase 3 Clinical Trial

Development of tirasemtiv halted due to poor performance in a late-stage clinical trial.

Cytokinestics, Inc recently announced that the VITALITY-ALS phase 3 clinical trial did not meet its primary or secondary endpoints in patients with amyotrophic lateral sclerosis (ALS), according to a press release.

The clinical trial evaluated the ability of investigational tirasemtiv to slow vital capacity (SVC) in patients with ALS at 24 weeks.

Secondary endpoints evaluated at 48 weeks included change in the score of the 3 respiratory items of the ALSFRS-R; score of muscle strength; time to decline from baseline in percent predicted SVC ≥20; onset of respiratory insufficiency or death; time to occurrence of a decline in SVC to ≤50%; change in the ALSFRS-R total score; and time to use of mechanical ventilatory assistance or death, according to the release.

The safety and tolerability profile for tirasemtiv was consistent with previous studies. The rate of adverse events was similar between the tirasemtiv and placebo cohorts, but more patients discontinued tirasemtiv than placebo due to tolerability issues, according to the release.

The investigators found that the reduction in SVC was lower in patients administered tirasemtiv compared with placebo patients receiving placebo, according to the study.

Cytokinetics notes that the most significant differences between the cohorts were observed in patients taking mid- and high-doses of tirasemtiv; however, the differences were not statistically significant, according to the release.

As a result of not meeting the study endpoints, the development tirasemtiv for ALS will be stopped.

“While we are deeply disappointed by the results of VITALITY-ALS, we remain committed to people with ALS who are fighting this devastating disease and who need new therapies to slow the decline of respiratory function and muscle strength that are key hallmarks of disease progression,” said Robert I. Blum, president and CEO at Cytokinetics. “We have decided to suspend the development of tirasemtiv. While we believe that VITALITY-ALS demonstrated pharmacologic activity for the mechanism of action, we also believe that limitations of tirasemtiv may be addressed with our next-generation fast skeletal muscle activator, CK-2127107. Based on previous Phase 1 clinical studies, we believe CK-2127107 will be better tolerated and potentially more effective than tirasemtiv in patients with ALS and look forward to Phase 2 trial results in 2018. We are grateful to the trial investigators, site personnel, patients and caregivers who participated in VITALITY-ALS.”