Pridopidine Maintains Effectiveness in Huntington Disease Without Antidopaminergic Medications


New findings from the phase 3 PROOF-HD trial showed that pridopidine outperformed placebo up to 78 weeks in patients with Huntington disease even after excluding those on neuroleptics and antichorea medications.

Jina Swarz, MD, PhD, chief medical officer at Prilenia

Jina Swarz, MD, PhD

Credit: Faculty of Pharmaceutical Medicine

New analyses from the phase 3 PROOF-HD trial (NCT04556656) showed that pridopidine (Prilenia Therapeutics), an orally available small molecule and potent sigma-1 receptor agonist in development for Huntington disease (HD), significantly improved or stabilized outcome measures for at least 1 year and displayed superiority to the placebo up to week 78 on all end points after excluding patients on antidopaminergic medication (ADMs).1 These findings suggest pridopidine still maintains benefit on several clinical measures of disease progression in patients with HD without the help of these therapies.

Excluding participants on ADMs (pridopidine, n = 79; placebo, n = 99), pridopidine-treated patients showed improvement from baseline on the Unified Huntington Disease Rating Scale (cUHDRS) up to week 52 and sustained benefit up to week 78 compared with placebo. Similarly, quantitative motor (Q-Motor) and Stroop Word Reading (SWR) improved from baseline at week 26 and sustained up to week 78 in comparison with the placebo. In addition, investigators observed a trend for improvement in Quality of Life (HD-QoL) also in this group of patients.

Top Clinical Takeaways

  • Pridopidine demonstrated significant improvement or stabilization in outcome measures for patients with Huntington disease over at least 1 year.
  • The exclusion of patients on antidopaminergic medication in the trial highlighted pridopidine's benefits across several clinical measures of disease progression.
  • Pridopidine's safety profile is comparable to placebo, suggesting its potential as a promising treatment option for Huntington disease.

“Pridopidine is now in preregistration phase in HD, with a first submission planned mid 2024, and is also set to commence a global phase 3 study in ALS later this year. We are making significant strides forward and this is reflected by presentation of the data at one of the most important medical congresses in the field of neurology,” Jina Swarz, MD, PhD, chief medical officer at Prilenia, said in a statement.2

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Michal Geva, PhD, senior vice president, head of research, Prilenia Therapeutics

Michal Geva, PhD

Credit: Prilenia Therapeutics

Presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, by lead author Michal Geva, PhD, senior vice president, head of research, Prilenia Therapeutics, and colleagues, PROOF-HD enrolled 499 patients with onset HD who had a Total Functional Capacity (TFC) scale score of at least 7. In the trial, the primary end point was the change from baseline to week 65 in TFC with key secondary end point that included change from baseline in the composite cUHDRS, a combined measure of motor function, cognition, and functional capacity. Additional end points investigators included were Q-Motor, cognition (SWR), and HD-QoL. The prespecified analyses excluded participants who had ADMs, including neuroleptics and antichorea medications, as their use may be associated with a worsening of disease progression.

A responder analysis of patients without ADMs revealed that pridopidine enhanced responder rates (5% improvement as threshold) across all visits for multiple key end points including cUHDRS, SWR, and Q-Motor. Thus, this analysis suggests that pridopidine demonstrated consistent and clinically meaningful separation of pridopidine at all timepoints and for key outcome measures. Overall, pridopidine was well tolerated with a safety profile comparable with placebo.

“Pridopidine is one of the most advanced investigational new drugs in HD and ALS and has shown consistent treatment benefits across independent measures that are important to patients and families,” Swarz said in a statement.2 “The presented data advances knowledge in the field, providing important learnings for both clinical practice and for the design of our programs going forward. This advance is evident with novel findings from studies showing benefit with pridopidine in those with HD who are not taking ADMs and a positive impact on speech and prolonged survival with pridopidine treatment in ALS.”

Click here for more coverage of AAN 2024.

1. Geva M, Reilmann R, Feigin A, et al. Analyses of the Phase 3 Trial of Pridopidine’s Outcome on Function in Huntington Disease (PROOF-HD) Demonstrates Efficacy in Participants Without Antidopaminergic Medications. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.
2. Prilenia to Present Latest Research from its Pridopidine Programs for Huntington Disease and ALS at AAN 2024. News Release. Prilenia Therapeutics. Published April 12, 2024. Accessed April 12, 2024.
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