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Results of a trial looking at the use of ropinirole hydrochloride for amyotrophic lateral sclerosis have been published in Cell Stem Cell.
Prof P Nigel Leigh FMedSci, Professor of Neurology, Brighton and Sussex Medical School, University of Sussex, said:
“This study is too small to say anything definitive about efficacy or even safety of this drug in ALS. The effect on ALSFRS-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) is only seen in the Open Label Extension (OLE) and OLEs are more likely to reflect imbalance in prognostic factors rather than a true drug effect. In other words, OLEs are more open to bias. There are differences in baseline demographics that are likely to influence prognosis of the disease. Overall, the study is too small for meaningful statistical analysis.
“Depending on the assumptions underlying power calculations, and in view of past experience, it is likely that one will need around 100 participants per treatment arm to see a credible change in ALSFRS-R slope of change over a minimum of 12 months.
“The riluzole trials that showed clear efficacy for survival at 18 months (with over 200 subjects per treatment arm) no significant effect was seen on function measured by the Norris scale- the ALSFRS-R did not exist then.
“There is so much variability in ALSFRS-R trajectories between subjects that only large numbers have a hope of showing a statistically robust and credible treatment effect using either slope of change or better, the joint rank analysis.
“It may be biologically plausible, as argued in the experimental biology section in this paper, for this drug to have a beneficial impact on ALS but considering the limitations mentioned above, this trial is unable to provide any meaningful answer as to whether there is a clinical effect in ALS patients.”
Prof Michael Swash, Professor of Neurology, Barts and the London School of Medicine, said:
“This is an interesting report. There has long been an effort to find an “off the shelf medication” applicable to ALS management. Ropinirole may be one such drug. But there needs to be a clearer understanding of its mechanism of action in order to apply such knowledge more widely. In addition, a larger study is required to understand who might benefit and what might be the limits of practical therapy in using ropinirole in ALS. More data on possible unwanted effects are also required. There are interesting parallels in proteinaceous accumulation in the neuronal cytosol between PD and ALS that should be explored.”
Dr Brian Dickie OBE, Director of Research at the MND Association, said:
“Whilst these results may be of some interest to the research community, the clinical trial is far too small and the findings too preliminary to draw any valid conclusions.”
‘Ropinirole hydrochloride for amyotrophic lateral sclerosis: A single-center, randomized, double blind, placebo-controlled phase 1/2a feasibility trial’ by Satoru Morimoto et al. was published in Cell Stem Cell at 16:00 UK time on Thursday 1 June.
DOI: https://doi.org/10.1016/j.stem.2023.04.017
Declared interests
Prof Michael Swash: “I have no conflicts relevant to this comment.”
For all other experts, no reply to our request for DOIs was received.