The U.S. Food and Drug Administration (FDA) has granted orphan drug status to Cytokinetics and Astellas Pharma‘s reldesemtiv for the treatment of amyotrophic lateral sclerosis (ALS), the companies announced.
Reldesemtiv, a fast skeletal muscle troponin activator designed to improve muscle function with minimal nerve stimulation, had already received the same designation from the FDA and European Medicines Agency for another motor disorder, spinal muscular atrophy (SMA).
The designation provides Cytokinetics and Astellas with benefits, including U.S. market exclusivity for seven years upon approval, FDA support for clinical studies, and special fee exemptions and reductions.
“We’re pleased that reldesemtiv received orphan designation from the FDA,” Fady I. Malik, Cytokinetics’ executive vice president of research & development, said in a press release.
The experimental therapy was studied in ALS patients in the randomized, double-blind FORTITUDE-ALS Phase 2 clinical trial (NCT03160898), which assessed the effects of reldesemtiv on respiratory function and other muscle function parameters in 458 patients with the condition.
Participants were recruited from centers across the U.S., Canada, Europe, and Australia, and randomly assigned to receive either reldesemtiv (at a dose of 150, 300 or 450 mg) or a placebo, orally twice a day, for 12 weeks.
FORTITUDE-ALS’ primary goal was to determine the changes in respiratory function, from study start to 12 weeks of treatment, measured with the percent predicted slow vital capacity (SVC).
Additional goals included changes in the ALS Functional Rating Scale Revised (ALSFRS-R, measuring the ability to perform daily functions such as speech, swallowing, and dressing), muscle strength, hand grip, plasma concentrations of reldesemtiv, and treatment-emergent adverse events (TEAEs) at week 12.
Patients receiving reldesemtiv (any dose) had smaller declines in their lung muscle function (27% lower), overall muscle strength, and existing abilities (ALSFRS-R) than those on a placebo, after 12 weeks of treatment. However, the results failed to reach statistical significance.
In a follow-up analysis, researchers evaluated the change in ALSFRS-R from baseline based on patients’ estimated rate of disease progression before entering FORTITUDE-ALS.
An analysis of patients with fast, middle, and slow progression showed that those with middle and fast progressing disease had a smaller decline in ALSFRS-R total score at the end of the 12 weeks when receiving any dose of reldesemtiv, compared to the placebo.
These results were statistically significant, according to the company. No significant differences were observed in patients with slowly progressing disease.
Patients treated with reldesemtiv also were 38% less likely to require the use of durable medical equipment, including wheelchairs, non-invasive ventilators, feeding tubes, and speech-generating devices.
In fact, a later analysis using Aural Analytics’ speech analytics platform technology found that reldesemtiv treatment slowed the decline in speech motor control, or the ability to articulate words, compared to the placebo. The analysis included 387 participants of FORTITUDE-ALS who provided speech samples over the treatment period.
“It’s an exciting time for the development of investigational medicines for ALS. We believe treatment with reldesemtiv may represent a complementary approach to other potential therapies by directly addressing impaired muscle function and weakness that affects patients with ALS,” Malik said.