PROOF-HD: Pridopidine benefits HD patients not taking antidopaminergics

medwireNews: The selective sigma-1 receptor agonist pridopidine improves functional, motor, and cognitive outcomes in patients with Huntington’s disease (HD) who are not taking antidopaminergic medications, suggests an analysis of the PROOF-HD study. “Pridopidine is the first drug to show clinically meaningful benefits across numerous measures of disease progression,” said Michal Geva, from Prilenia Therapeutics in Naarden, the Netherlands in an ePresentation at the 10th Congress of the European Academy of Neurology. The phase 3 trial randomly assigned 499 patients with HD who had a baseline Total Functional Capacity scale score of at least 7 points to receive either pridopidine 45 mg twice a day or placebo. The prespecified subgroup analysis presented to delegates in Helsinki, Finland, included 178 of the study participants who were not taking antidopaminergic medications, of whom 79 received pridopidine and 99 placebo. A significant improvement in the composite Unified Huntington’s Disease Rating Scale (uHDRS) was seen from baseline up to week 52 of treatment with pridopidine, whereas “the placebo group declines predictably,” said the presenter. The least squares mean treatment differences were a significant 0.46 points at week 26, 0.60 points at week 39, and 0.43 points at week 52, all in favor of pridopidine treatment. This improvement was sustained to week 78, at which time, the treatment difference was a significant 0.50 points. Geva noted that a decrease of 0.2–0.3 points a year on the cUHDRS, equivalent to a 20% to 30% decline, is generally considered “clinically efficacious.” She added that a significant benefit with pridopidine versus placebo was seen across all four components of the scale, including Total Functional Capacity, Total Motor Score, and the two cognition tests, the Stroop Word Reading Test and the Symbol Digit Modalities Test, “demonstrating that impact [was not] driven by one domain and not by chance,” said Geva. Secondary endpoints supported the findings, with significant improvement from baseline with pridopidine up to 78 weeks of treatment versus a decline with placebo on the quantitative Q-motor finger tapping measure. The least squares mean treatment differences were a significant 31.96 msec at week 26, 22.84 msec at week 39, through to a significant 34.23 msec at week 78. Similarly, cognition (sharp-wave ripple) improved from baseline to week 78 among patients taking pridopidine but not those taking placebo. The least squares mean differences between the two treatments were a significant 3.32 points at week 26, 4.14 points at week 39, and 4.22 points at week 52, and this was maintained at week 72 at 2.82 points. The presenter summarized: “PROOF-HD results show consistent beneficial effect in patients off-antidopaminergics.” She added that benefits were seen across “multiple independent clinical endpoints that matter most to patients and families.” medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group EAN Congress 2024; Helsinki, Finland: 29 June–2 July

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PROOF-HD: Pridopidine benefits HD patients not taking antidopaminergics

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