Objective: Assess the efficacy of pridopidine 45 mg bid for maintenance of total functional capacity (TFC) and motor function in early HD patients.

Background: Pridopidine is a potent Sigma-1 Receptor (S1R) agonist in clinical development for HD and ALS. S1R is an ER-mitochondrial chaperone regulating key pathways commonly impaired in neurodegeneration including BDNF secretion, Ca²⁺ signaling and mitochondrial function. Preclinically, pridopidine enhances BDNF secretion and synaptic plasticity. In humans, PET imaging confirms that 45 mg BID pridopidine has robust and selective S1R occupancy. In PRIDE-HD, a phase 2 dose-ranging study, the effects of pridopidine in HD patients were assessed over 52 weeks.
TFC is a widely accepted scale used by clinicians to measure HD stage and functionality, and an important measure for HD patients. Decline in TFC is steepest in early HD patients and associates with other aspects of disease progression including brain atrophy, motor dysfunction, and behavioral abnormalities.

Method: Post-hoc exploratory analysis of the 45 mg bid dose from PRIDE-HD in early HD patients determined the effect of pridopidine on TFC and motor measures including dystonia. Robustness of pridopidine’s effect on TFC was assessed by using the most conservative analysis assuming worst case scenario Missing Not At Random (MNAR). Additional motor and behavioral clinical measures were also assessed.

Results: Pridopidine 45 mg BID shows maximal effect on TFC at week 52 (Δ0.87 from placebo, nominal p=0.0032). Post-hoc analysis shows this effect is most evident in early HD patients (HD1+HD2, baseline TFC 7-13) (Δ1.16 from placebo, p=0.0003). Using MNAR, pridopidine maintains a beneficial effect at 52 weeks (nominal p=0.016). Furthermore, a post-hoc responder analysis demonstrates fewer patients treated with 45 mg BID pridopidine have TFC worsening (ΔTFC<0) vs placebo (18.9% vs 51.2%, p=0.002). Additionally, in patients for whom UHDRS-TFC change was ≥0, there was significant benefit in additional clinical measures.

Conclusion: These data strongly suggest that pridopidine 45mg BID is efficacious for maintaining TFC in early-stage HD for the 52-weeks duration assessed in PRIDE-HD.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/pridopidine-for-the-treatment-of-early-huntingtons-disease/