Background: No pharmacological treatment has been demonstrated to provide a functional benefit for persons with Huntington's disease (HD). Pridopidine is a sigma-1-receptor agonist shown to have beneficial effects in preclinical models of HD.
Objective: To further explore the effect of pridopidine on Total Functional Capacity (TFC) in the recent double-blind, placebo-controlled PRIDE-HD study.
Methods: We performed post-hoc analyses to evaluate the effect of pridopidine on TFC at 26 and 52 weeks. Participants were stratified according to baseline TFC score and analyzed using repeated measures (MMRM) and multiple imputation assuming missing not-at-random (MNAR) and worst-case scenarios.
Results: The pridopidine 45 mg bid dosage demonstrated a beneficial effect on TFC for the entire population at week 52 of 0.87 (nominal p = 0.0032). The effect was more pronounced for early HD participants (HD1/HD2, TFC = 7-13), with a change from placebo of 1.16 (nominal p = 0.0003). This effect remained nominally significant using multiple imputation with missing not at random assumption as a sensitivity analysis. Responder analyses showed pridopidine 45 mg bid reduced the probability of TFC decline in early HD patients at Week 52 (nominal p = 0.02).
Conclusion: Pridopidine 45 mg bid results in a nominally significant reduction in TFC decline at 52 weeks compared to placebo, particularly in patients with early-stage HD.
Keywords: Huntington’s disease; clinical trial; pridopidine; total functional capacity.