Effects of Pridopidine on Functional Capacity in Early-Stage Participants from the PRIDE-HD Study

Andrew McGarry, Mika Leinonen, Karl Kieburtz, Michal Geva, C Warren Olanow, Michael Hayden, Andrew McGarry, Mika Leinonen, Karl Kieburtz, Michal Geva, C Warren Olanow, Michael Hayden

Abstract

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.

Conflict of interest statement

AM and KK have previously received grant support from Teva. MG and MH are previous employees of Teva. AM, KK, CWO are consultants for Prilenia therapeutics.

Figures

Fig. 1
Fig. 1
TFC change from baseline vs. placebo for pridopidine 45 mg bid at Weeks 26 and 52 in All Participants (A,B) and Early HD patients (C,D). Mean±SEM; p-values are nominal and presented for descriptive purposes only. (E) Change in TFC plotted over time in early HD (TFC≥7); *p = 0.036; **p = 0.0003.
Fig. 2
Fig. 2
Mean TFC change from baseline vs. placebo at Week 52 for all participants and early HD cohorts (TFC 7–13): comparison of MMRM to MNAR. Magnitude and p-value for the change in TFC, 45 mg BID vs. placebo, at 52 weeks.

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