Ropinirole use in amyotrophic lateral sclerosis (ALS) significantly delays the time to the first disease progression, according to a recent, but small, randomised placebo-controlled trial with an open-label extension phase.
ALS is a rare neurological disease affecting motor neurons (MNs) in the brain and spinal cord that control voluntary muscle movement. ALS is also a progressive disease characterised by muscle atrophy and weakness caused by selective vulnerability of MNs. In Europe, only one drug, riluzole is licensed for the treatment of ALS. Ropinirole is a dopamine D2 receptor agonist that is approved for the use in the treatment of Parkinson’s disease. However, recently, drug-based screening studies have revealed how ropinirole may also be effective in ALS.
In the current study, published in the journal Cell Stem Cell, Japanese researchers conducted a phase 1/2a, randomised, double-blind, placebo-controlled trial, followed by an open-label extension, of ropinirole in patients with ALS. A total of 20 patients with sporadic ALS received either ropinirole or placebo (3:1) for 24 weeks in the double-blind phase of the study, in which safety, tolerability and the therapeutic efficacy were assessed. This was followed by a four- to 24-week open-label extension study in which patients originally assigned to placebo switched to ropinirole.
For the study, a number of parameters were assessed with the primary outcome based on adverse events. In total, there were 11 secondary outcomes including functional outcomes such as the revised ALS functional rating scale (ALSFRS-R) score, which assessed patient’s disability; survival; and time to the first disease progression event.
Effect of ropinirole on functional outcomes
In the 24-week double-blind part of the trial, 13 patients received ropinirole and seven a placebo. There was no significant difference in the overall incidence of adverse events (92.3% vs 85.7%, ropinirole vs placebo). In addition, there was no significant effect of treatment on ALSFRS-R scores (mean between group difference, MBGF = 1.46, 95% CI -3.15 to 6.07).
However, beyond the initial 24-week period, there was a persistent increase in between-group differences in ALSFRS-R scores (MBGF = 9.86, 95% CI 4.07 – 15.66, p < 0.001). Differences in survival favouring ropinirole occurred but were only apparent during the open-extension phase. However, across the whole trial period, this difference was significant (median difference = 9.0, 95% CI 1 – 12).
One of the most impressive findings was how the ropinirole group had a longer period of time (27.9 weeks) before their first disease progression event (p = 0.008).
The authors estimated the effect size of ropinirole on the ALSFRS-R score over 48 weeks to be 1.46 to 9.86. This translated into a 21-60% slower rate of functional decline, which was considered to be clinically meaningful. Nevertheless, they recognised that the small sample size – of 18 completing the 24-week double-blind phase and only eight completing the extension phase – limited the generalisability of their findings.