Cytokinetics has reported negative results from its international phase 3 VITALITY-ALS trial to test the investigational drug tirasemtiv in people with ALS.
The goals of the study were to assess the effects of tirasemtiv versus a placebo on respiratory function and muscle strength. Investigators assessed slow vital capacity (SVC), a measure of breathing function, as well as other measures of respiratory function and muscle strength.
The trial missed its primary endpoint of change from baseline in SVC after 24 weeks of treatment with tirasemtiv as compared to placebo.
Based on these results, Cytokinetics has announced it will suspend the development of tirasemtiv.
Tirasemtiv is a skeletal muscle activator that is designed to increase the sensitivity of muscle fibers to calcium, which should cause these fibers to contract even if the signal from the nervous system is weaker than normal. In preclinical studies and early clinical trials, it demonstrated increases in skeletal muscle force and reductions in the degree of muscle fatigue.
While this approach does not address the underlying cause of ALS, drugs that utilize this strategy potentially could help strengthen the breathing muscles in people with ALS, possibly extending the time a person could breathe independently without the need for ventilatory assistance.
Tirasemtiv has been studied in clinical trials that have enrolled over 1000 people internationally.
New directions: CK-2127107
Although the negative results in the phase 3 ALS trial are disappointing, Cytokinetics reported that it has a second-generation drug called CK-2127107, which is thought to work through the same biological mechanism as tirasemtiv and may be better tolerated and more effective than tirasemtiv.
CK-2127107 has been tested in five completed phase 1 clinical trials in healthy volunteers, in which the safety, tolerability, bioavailability, pharmacokinetics and pharmacodynamics of the drug were assessed. CK-2127107 currently is being developed for neuromuscular and non-neuromuscular diseases and conditions associated with muscle dysfunction and weakness.
CK-2127107 currently is in phase 2 trials for ALS and spinal muscular atrophy (SMA).
For more information
If you participated in Vitality-ALS, or the extension study VIGOR-ALS, and you have questions, be sure to speak with your physician, and remember to check back at mda.org for updates.