COURAGE-ALS Trial of Reldesemtiv to Continue After Interim Analysis

Study into therapy's safety, efficacy versus placebo in up to 555 ALS patients

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The COURAGE-ALS Phase 3 trial of Cytokinetic’s experimental therapy reldesemtiv in people with amyotrophic lateral sclerosis (ALS) will continue as planned following its first planned interim analysis.

A data monitoring committee met to review the trial’s data so far with the goal of assessing futility, or whether the likelihood of reldesemtiv meeting the trial’s goals was too low to move forward. Following its analysis, the committee recommended the trial continue, according to a press release from Cytokinetics.

Reldesemtiv, developed by Cytokinetics in partnership with Astellas, works to activate the troponin protein in a type of muscle called fast-twitch fibers, which mediate quick, powerful movements such as sprinting or eye blinking.

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By activating troponin, reldesemtiv is thought to increase muscles’ ability to respond to weak nerve signals, thereby slowing the progressive muscle weakness that’s a feature of ALS and other neuromuscular diseases.

The investigational treatment has received orphan drug designation in the U.S. and Europe, as well as fast-track status in the U.S. Both are meant to speed reldesemtiv’s clinical development and regulatory review.

COURAGE-ALS (NCT04944784) is evaluating reldesemtiv’s safety and effectiveness against a placebo in up to 555 adults whose ALS symptoms began in the last two years and who show moderate-to-fast disease progression.

Participants must also have moderate lung function decline and an ALS Functional Rating Scale Revised (ALSFRS-R) score of 44 or lower at enrollment. ALSFRS-R scores range from zero to 48, with lower scores indicating worse disability. A score of 44 reflects mild functional disability.

Recruitment is ongoing at nearly 80 sites in North America, Europe, and Australia.

This specific patient subgroup was chosen based on findings from the FORTITUDE-ALS Phase 2 trial (NCT03160898). While the study failed to meet its efficacy goals of significantly slowing lung and functional declines, participants with a shorter disease duration and moderate-to-fast progression showed the greatest benefits from reldesemtiv.

COURAGE-ALS participants are randomly assigned in a 2:1 ratio to receive an oral tablet of either reldesemtiv (300 mg) or a placebo, twice daily for 24 weeks, or about six months. Following the completion of the trial’s initial part, all participants will receive reldesemtiv for another 24 weeks.

Patients on stable doses of standard ALS medications Radicava (edaravone) and/or riluzole (sold as Rilutek, Tiglutek, or Exersan) may continue treatment during the study.

Assessing reldesemtiv’s ability to slow ALS progression

The primary goal of COURAGE-ALS is to assess the treatment’s ability to slow disability progression, as assessed by changes in ALSFRS-R scores, after the first 24 weeks.

Secondary goals include changes in lung function, grip strength, and quality of life, as well as combined changes in functional status, time to respiratory insufficiency, and death.

The first planned interim analysis was about 12 weeks after a third or more of the intended number of patients had been assigned a treatment group.

While data from the trial’s placebo-controlled part are double-blinded, meaning neither the investigators nor the participants know which patients got the medication, the monitoring committee can assess the data unblinded in order to determine its effects.

A second interim analysis is expected in the first half of 2023. It will assess for potential futility, as well as allow for an increase in total enrollment, if deemed necessary to increase statistical power. The trial is expected to finish in March 2024.

After completing it, participants will be given the choice to enroll in its open-label extension study called COURAGE OLE (NCT05442775), wherein the therapy will be continued for another 48 weeks (nearly one year).

In the extension study, the primary goal will be to evaluate the treatment’s safety, with secondary efficacy goals including changes in the ALSFRS-R score, time to respiratory insufficiency or death, and time to first hospitalization.

Those completing the COURAGE OLE study will be able to continue treatment under Cytokinetic’s Managed Access Program. Also known as a compassionate use program, it allows reldesemtiv trial participants access to the therapy ahead of regulatory approval.