Integrative Research Laboratories Sweden AB’s (IRLAB) Phase IIb REACT-PD trial results for pirepemat highlight both the promise and the complexity of targeting non-dopaminergic symptoms in Parkinson’s disease (PD), particularly falls and balance impairment, which remain major unmet needs, says GlobalData, a leading intelligence and productivity platform.

Presented at the AD/PD 2026 International Conference, the REACT-PD study evaluated pirepemat, an oral small molecule designed to enhance cortical neurotransmission by increasing synaptic dopamine and norepinephrine in the prefrontal cortex. This approach targets mesocortical dysfunction linked to executive impairment and postural instability, both key contributors to falls in PD.

Graysen Vigneux, Pharma Analyst at GlobalData, comments: “Falls, gait disturbances, and cognitive impairment remain difficult to manage with current dopaminergic therapies, highlighting a clear need for novel treatments targeting non-dopaminergic pathways. Pirepemat introduces a novel cortical-targeted approach in PD, with exposure–response data suggesting that efficacy may depend on precise dosing rather than fixed regimens.”

The randomized, placebo-controlled REACT-PD study enrolled 104 patients across 38 European sites, evaluating 300 mg and 600 mg doses over 12 weeks. Although the 600 mg group showed a 42% reduction in fall rate, this did not reach statistical significance versus placebo, highlighting variability with fixed dosing.

A pharmacokinetic/pharmacodynamic analysis revealed a U-shaped exposure–response relationship, with the mid-exposure group achieving a statistically significant 31% reduction in falls (p<0.05), while low- and high-exposure groups showed no significant benefit. Improvements were not associated with changes in motor scores (MDS-UPDRS), supporting a non-dopaminergic mechanism.

Vigneux concludes: “The REACT-PD findings underscore both the opportunity and challenges of addressing non-dopaminergic symptoms in PD. With optimized dosing, pirepemat could emerge as a novel option in an area of high unmet need. However, this could present practical challenges in clinical adoption, as individualized dosing may require additional monitoring and titration compared to standard fixed-dose therapies.”