An oral drug may cut Parkinson’s falls when it reaches the right blood level, according to clinical trial data presented in Europe.
Falls are among the most common and serious complications of Parkinson’s, driven by balance and gait problems, and there is currently no satisfactory treatment.
The Phase 2b trial tested pirepemat, an experimental therapy designed to reduce falls by strengthening nerve cell signalling in the brain.
The trial enrolled 104 adults with Parkinson’s, who were randomly assigned to receive either 300mg or 600mg of pirepemat or a placebo for 12 weeks.
A total of 90 participants completed treatment.
The therapy was developed by Swedish company Irlab Therapeutics. The company said topline results showed a marked reduction in fall rates across all treatment groups, but no statistically significant difference versus placebo.
A study abstract presented at the meeting reported that patients given the 600mg dose had a 42 per cent reduction in fall rate compared with placebo, but this did not reach statistical significance.
Further analysis split pirepemat-treated patients into three groups based on minimum blood levels before the next dose.
Those in the middle exposure range saw a significant 31 per cent reduction in fall rates compared with placebo, equal to seven fewer falls a month.
Patients with lower and higher concentrations of the drug in their blood did not see a significant reduction in falls. The apparent benefit at the optimal concentration was not linked to changes in motor or balance assessments.
The findings were presented at the AD/PD Alzheimer’s and Parkinson’s Diseases Conference, held from 17 to 21 March in Copenhagen, Denmark.
Irlab stated: “Pirepemat, in an optimal plasma concentration range, could significantly and clinically meaningfully reduce falls in PD [Parkinson’s disease].”
At the same conference, Irlab also shared findings on real-world use of amantadine for levodopa-induced dyskinesia, meaning uncontrolled, involuntary movements that can develop as a side effect of long-term levodopa use.
Levodopa is the most effective treatment for easing Parkinson’s motor symptoms.
Drawing on data from PPMI, an international registry study on Parkinson’s progression and biomarkers, the analysis of 1,340 participants found that about one-third reported dyskinesia at their last visit and that 29 per cent of those patients were treated with amantadine.
Most were receiving daily doses below the recommended effective level.
Those treated with amantadine were more likely to have LRRK2, one of the most common genetic causes of Parkinson’s, and tended to have more severe Parkinson’s symptoms, including dyskinesia, cognitive impairment and more difficulty with daily activities.
Motor function was generally better among those treated with amantadine, as assessed by clinicians using the MDS-UPDRS part 3 score, although one-third of patients who started treatment later stopped.
Those who discontinued generally had more severe symptoms than those who continued.
In another poster, the company also presented behavioural assessment tools being developed through its Integrative Screening Process, an AI and machine learning drug discovery platform.
It combines data from animal models, human tissue samples and lab studies to help predict compounds with potential for specific diseases.
Irlab said the latest advance uses AI to identify behavioural measures captured through video recordings, which may help predict response to new compounds more accurately.
The company said several programmes derived from the platform are now in development, including pirepemat for falls, mesdopetam for levodopa-induced dyskinesia and a project exploring once-daily oral dopamine receptor agonists for Parkinson’s motor symptoms.
