The move follows fast track designation granted in December by the U.S. Food and Drug Administration for the same indication, and provides the company with various incentives. Those include assistance in developing trial protocols and a 10-year period of market exclusivity once the treatment is approved.
Reldesemtiv holds the same designation both from EMA and the FDA for another motor disorder, spinal muscular atrophy (SMA).
“Receipt of orphan status in Europe builds on the orphan status we received in the U.S., reinforcing the continued unmet need for patients in these key regions who are combating weakening muscle function and the relentless challenges related to ALS,” Fady I. Malik, MD, PhD, Cytokinetics’ executive vice president of research and development, said in a press release.
Reldesemtiv, being developed by Cytokinetics in collaboration with Astellas Pharma, is a fast skeletal muscle troponin activator (FSTA) meant to ease muscle contraction with minimal nerve stimulation to slow the decline of muscle function associated with ALS and other neuromuscular diseases.
The investigational treatment was assessed in ALS patients in the completed FORTITUDE-ALS study (NCT03160898), a randomized Phase 2 trial that compared the effects of reldesemtiv to a placebo in patients diagnosed less than two years before entering the study.
A total of 458 patients were randomly assigned to receive increasing doses of reldesemtiv — 150, 300 or 450 mg — or a placebo, given orally twice a day for 12 weeks. Those receiving the standard ALS therapy riluzole before enrolling could continue doing so during the trial.
The trial’s main objective was to determine changes in respiratory function, from study start to 12 weeks of treatment, measured as 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 adverse events at week 12.
While reldesemtiv slowed the decline in lung function and overall disease worsening compared with a placebo, the results failed to meet statistical significance, meaning the trial did not meet its primary or secondary endpoints.
However, a follow-up analysis showed that when patients were grouped based on their rates of disease progression before entering FORTITUDE-ALS – fast, middle, or slow – those with middle and fast progression had a significant benefit from reldesemtiv.
In fact, at the end of the 12-week treatment, these patients had a smaller decline in ALSFRS-R total score when given reldesemtiv relative to placebo. No significant differences were observed in patients with slowly progressing disease.
Patients treated with reldesemtiv were also 38% less likely to need durable medical equipment, including wheelchairs, non-invasive ventilators, feeding tubes, and speech-generating devices.
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