The additional analyses were presented by the trial’s principal investigator, Jeremy M. Shefner, MD, PhD, a professor at the Barrow Neurological Institute and the University of Arizona, at the 2019 Northeast Amyotrophic Lateral Sclerosis (NEALS) meeting, in Clearwater Beach, FL.
FORTITUDE-ALS was a randomized, double-blind, placebo-controlled, Phase 2 trial (NCT03160898) that assessed the effects of reldesemtiv on respiratory function and other muscle function parameters in people with ALS. A total 458 patients, recruited from centers across the U.S., Canada, Europe, and Australia, were randomly assigned to either reldesemtiv (at a dose of 150, 300 or 450 mg) or a placebo, taken orally, twice a day, for 12 weeks.
Primary data analysis showed that all doses of reldesemtiv led to small improvements in the percent predicted slow vital capacity (SVC), a standard measure of respiratory function, compared with a placebo after 12 weeks of treatment. However, the results failed to reach statistical significance. Change from the study’s start in the ALS Functional Rating Scale Revised (ALSFRS-R) and overall muscle strength led to similar findings.
In the latest post-hoc analyses, the researchers evaluated the change in ALSFRS-R from baseline based on patients’ estimated rate of disease progression prior to the study’s start.
Patients were divided into faster, middle, and slower progression tertiles, based on their onset date of ALS symptoms and their ALSFRS-R total score at baseline.
Results of these analyses showed that, in patients with middle and fast progressing disease, the decline in ALSFRS-R total score was smaller in patients who received any dose of reldesemtiv, compared with those taking the placebo, at the end of the 12 weeks. These results were statistically significant, according to the company.
In contrast, no significant differences were observed in patients with slowly progressing disease.
Additionally, the use of durable medical equipment, including manual or electric wheelchairs, non-invasive ventilators, feeding tubes, and speech-generating devices, was less common in all groups treated with reldesemtiv. Among all dosing groups, the patients treated with reldesemtiv were 38% less likely to need this type of equipment, compared to patients on placebo. This indicates that reldesemtiv may have an impact on the timing and use of equipment, which suggests a potential clinical benefit for patients, Cytokinetics said in a news release.
“It’s encouraging to see that faster and middle progressing tertiles of patients treated with reldesemtiv experienced a significant slowing of disease progression,” said Fady I. Malik, MD, PhD, Cytokinetics’ executive vice president of research and development.
“These data indicate that, although FORTITUDE-ALS did not achieve statistical significance in the primary analysis of change from baseline in slow vital capacity (SVC) or a similar analysis for ALSFRS-R, favorable outcomes of treatment with reldesemtiv appear evident in more rapidly progressing patients, which supports continued evaluation of reldesemtiv as a treatment for patients with ALS,” Malik added.
In other news, Cytokinetics recently announced a call for proposals for the Cytokinetics Communications Fellowship Grant program, which offers a total of $100,000 in grants to five selected patient advocacy organizations serving the ALS, heart failure, hypertrophic cardiomyopathy, or spinal muscular atrophy communities.
The goal of these fellowships is to support the organizations in their communications, awareness, and outreach efforts. The deadline to apply is Nov. 15, 2019, and the grant recipients will be announced in January 2020. For more information, visit the official site here.