Tirasemtiv not found effective for treatment of MND

In their official press release published on 21 November 2017, Cytokinetics Inc. announced that they will not be continuing work on tirasemtiv after disappointing results in the latest Phase 3 clinical trial. The trial, known under the acronym ‘VITALITY-ALS’, tested whether the drug has a beneficial effect on the breathing function and muscle strength of people with MND. This is very unfortunate news for everyone affected by the disease, however, Cytokinetics are already testing another compound with the hope that this will be more effective and better tolerated than tirasemtiv.

Tirasemtiv is a drug that aims to improve quality of life of people living with MND by increasing strength of their skeletal muscles (controlling body motion and posture) and therefore postponing muscle fatigue. It compensates for the missing nerve signal from a motor neurone to a muscle that instructs it to contract. Tirasemtiv activates a protein called troponin by increasing its sensitivity to calcium, which is crucial for muscle contraction.

Results of the latest Phase 3 study

After observing some significant results in the decrease of slow vital capacity (SVC; a measure of strength of the muscles involved in breathing) and improvement of muscle strength, the double-blind, placebo-controlled VITALITY-ALS trial was hoped to confirm these findings. Six hundred people with MND across the world were randomised into groups receiving various doses of tirasemtiv (to assess the ideal dosage of the drug), or placebo. All participants were given either tirasemtiv or placebo twice daily for 48 weeks, alongside with their normal course of treatment with riluzole (in some participants, the dose of riluzole may have been reduced).

The primary outcome, that was amended based on the results of the previous study, was a change in the predicted percentage of SVC from baseline to week 24. Although the decline in SVC was smaller in people receiving tirasemtiv compared to those on placebo, these results were not shown as being statistically significant.

What is next?

People involved in the VITALITY-ALS study were offered participation in an ‘open-label’ study, in which everyone is offered tirasemtiv, to observe long-term effects of the treatment.

While it is disappointing that tirasemtiv failed to make it to the list of treatments we all hope to be available to use in the future, Cytokinetics are now looking at safety of the next-generation compound ‘CK-107’ in a Phase 2, double-blind, placebo-controlled clinical trial FORTITUDE-ALS. Similar to tirasemtiv, this treatment aims to improve breathing and skeletal muscle function in people with MND, with reduced adverse effects. We will be watching the progress of this treatment closely and report on any updates that will come up in the future.

 

3 thoughts on “Tirasemtiv not found effective for treatment of MND

    • Troponin exists in different forms – cardiac-specific troponin is structurally different from troponin occuring in skeletal muscles and therefore works in a slightly different way. Cardiac troponin is released when heart muscle cells die and so its presence in the blood can indicate heart damage. Skeletal troponin promotes muscle contraction only in our ‘voluntary control’ muscles.

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