Reldesemtiv Slowed Disease Progression in Trial Participants With Relatively Faster Progressing Amyotrophic Lateral Sclerosis
Post hoc analysis of the phase 2 FORTITUDE-ALS trial (NCT03160898) suggests some participants with amyotrophic lateral sclerosis (ALS) treated with reldesemtiv (Cytokinetics, San Francisco, CA) had slowed disease progression.
In post-hoc analyses, the change in the ALS Functional Rating Scale–Revised (ALSFRS-R) total score from baseline was compared among participant groups, defined by estimated rate of prestudy rates of disease progression defined as the slow-, medium-, and fast-progressing third of 458 participants. Participants in the middle- and fast-progressing tertiles treated with reldesemtiv had smaller declines in total ALSFRS-R score from baseline to week 12 compared with those treated with placebo (LS mean treatment difference 1.15, P = .011). In contrast, in participants in the slowest progressing third, no significant difference was seen in those who received reldesemtiv vs placebo.
“It’s encouraging to see that faster-progressing and middle-progressing tertiles of patients treated with reldesemtiv experienced a significant slowing of disease progression,” said Fady I. Malik, MD, PhD, executive vice president, research and development, Cytokinetics. “These data indicate that, although FORTITUDE-ALS did not achieve statistical significance in the primary analysis of change from baseline in 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.”
The FORTITUDE-ALS trial was a double-blind, placebo-controlled study in patients with ALS. In the study, 458 ALS patients were randomized to receive 150 mg, 300 mg, or 450 mg of reldesemtiv or placebo orally twice daily for 12 weeks. When reldesemtiv treatment was compared to placebo across the entire cohort of participants, the primary efficacy endpoint of change from baseline in predicted respiratory function was not met.