Cytokinetics Adds Decade of Trial Findings to PRO-ACT Database

ALS research can benefit from this large source of de-identified patient records

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by Mary Chapman |

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The Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database, the largest collection of de-identified records on amyotrophic lateral sclerosis (ALS) patients in clinical trials, has been updated with records of participants in three Cytokinetics-sponsored studies.

Newly added findings derive from a decade of trials involving nearly 600 ALS patients. Those studies include the BENEFIT-ALS (NCT01709149) and VITALITY-ALS (NCT02496767) trials, which investigated the treatment candidate tirasemtiv in people with ALS, as well as the FORTITUDE-ALS (NCT03160898) trial that tested reldesemtiv.

A separate Phase 3 trial of reldesemtiv in people with moderate-to-fast progressing disease but recent symptoms is also underway and enrolling globally.

“We are pleased to share these data with the ALS community to further research, understanding, and potential breakthroughs for people living with this grievous disease,” Fady I. Malik, MD, PhD, executive vice president of research and development at Cytokinetics, said in a company press release.

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“We recognize that we all benefit from shared insights, successes, and even failures if we are going to ultimately make a difference in the lives of many. We thank the people living with ALS who participated in our clinical trials to make this possible,” Malik added.

ALS researchers can freely access PRO-ACT

The PRO-ACT database is sponsored by the ALS Association and managed by the Neurological Clinical Research Institute at Massachusetts General Hospital. It contains more than 11,000 records, stripped of identifying information, on ALS patients who took part in 23 completed clinical studies to date.

Currently, PRO-ACT has more than 10 million data points collected from patients over time, including their demographics, laboratory and medical results, and family history.

These data are freely available to the scientific community for use in research. The PRO-ACT database was awarded the $50,000 Healey Center Prize for Innovation in ALS last year.

The Phase 2 BENEFIT-ALS trial evaluated tirasemtiv, designed to improve muscle strength in ALS patients by activating troponin, a protein found in voluntary muscles, in 711 patients from eight countries.

Results from BENEFIT-ALS showed that tirasemtiv significantly slowed the decline in muscle strength and respiratory function, although the treatment failed the primary goal of delaying disability progression.

The Phase 3 VITALITY-ALS trial evaluated three doses of tirasemtiv in an initial group of 565 ALS patients. Findings showed that patients who tolerated higher doses of the experimental treatment demonstrated a trend toward a slower decline in lung function.

These differences were still not statistically significant, and other measures of disease progression also showed no distinction between patients on tirasemtiv and placebo. Cytokinetics suspended work on tirasemtiv in 2017 when the study failed its primary and secondary objectives.

FORTITUDE-ALS, a Phase 2 clinical trial, assessed reldesemtiv, a next-generation fast skeletal muscle troponin activator, in 458 ALS patients. Results found it slowed respiratory and physical function decline in treated patients relative to those on placebo. But differences measured were not statistically significant, and the trial failed to meet its primary and secondary objectives.

Further analyses, however, showed that patients with moderate-to-fast ALS progression at trial entry could benefit significantly from reldesemtiv.

Cytokinetics then opened a global Phase 3 trial, called COURAGE-ALS (NCT04944784), which is evaluating reldesemtiv against a placebo in up to 555 ALS patients with anticipated moderate-to-fast disease progression and whose first symptoms were within the previous two years. Its primary goal is changes in the ALS Functional Rating Scale-Revised (ALSFRS-R), a standard measure of disease progression, from the study’s start to week 24 (about six months).

The trial is still recruiting eligible adults at centers in the U.S., Canada, Europe, and Australia; contact and site information is available. As such, no decision has been made as to whether its findings might be added to PRO-ACT at a future date.

Patients who complete the 48-week the COURAGE-ALS trial will be invited to join an open-label extension study into reldesemtiv’s safety and efficacy. Extension study patients will be treated for an additional 48 weeks.

“We are grateful to Cytokinetics for their partnership and transparency, enabling the global research community to leverage these data in their ongoing analyses and research activities,” said Neil Thakur, PhD, chief mission officer at the ALS Association.