Hypothesis
Pridopidine would slow functional decline in early-stage manifest Huntington's disease, measured by total functional capacity and the composite UHDRS at week 65.
What failed
Neither the primary nor the key secondary endpoint was met in the overall population: total functional capacity difference versus placebo was −0.18 (95% CI −0.49 to 0.14, P = 0.26) and the composite UHDRS difference was −0.11 (95% CI −0.40 to 0.18, P = 0.45).
Broken assumption
Sigma-1 receptor agonism slows functional decline in early manifest Huntington's disease.
Why
The paper reports a consistent pattern favouring pridopidine in a sensitivity analysis of participants never taking antidopaminergic medication, which it treats as a hypothesis, and notes the 45 mg twice-daily dose was well tolerated.
From the published paper: Reilmann et al. Nature Medicine, 2025. ↗CC BY