Abstract Details

Title Analyses of the Phase 3 Trial of Pridopidine’s Outcome on Function in Huntington Disease (PROOF-HD) Demonstrates Efficacy in Participants Without Antidopaminergic Medications

Topic Movement Disorders

Presentation(s) S30 - Movement Disorders: Clinical Trials in Movement Disorders (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

Background

Pridopidine is an orally available small molecule and potent sigma-1 receptor agonist.

Objective

The efficacy and safety of pridopidine was assessed for the treatment of Huntington Disease (HD) in the phase 3 trial, PROOF-HD.

Design/Methods PROOF-HD enrolled 499 adult-onset HD participants (Total Functional Capacity (TFC) ≥7). The primary endpoint was change from baseline to week 65 in TFC. The key secondary endpoint was change from baseline in the composite Unified Huntington Disease Rating Scale (cUHDRS), and additional endpoints included quantitative motor (Q-Motor), cognition (Stroop Word Reading (SWR)), and Quality of Life (HD-QoL). Prespecified analyses excluded participants on antidopaminergic medication (ADMs) (neuroleptics and anti-chorea medications) as their use may be associated with a worsening of disease progression.

Results Pridopidine was well tolerated with a safety profile comparable to placebo. The primary endpoint was not met. In analyses excluding participants on ADMs (placebo n=99, pridopidine n=79), pridopidine shows improvement from baseline in cUHDRS, a combined measure of motor function, cognition, and functional capacity up to week 52 and sustained benefit up to week 78. Q-Motor and SWR are improved from baseline at week 26 and sustained up to week 78. A trend for improvement in HD-QoL is also observed in this group. A responder analysis of participants excluding ADMs demonstrates that pridopidine enhances responder rates (5% improvement as threshold) across all visits for multiple key endpoints including cUHDRS, SWR, and Q-Motor.

Conclusions

In analyses excluding participants on ADMs, pridopidine significantly improves or stabilizes all outcome measures for at least 1 year and was better than placebo up to week 78 for all endpoints. A responder analysis demonstrates consistent and clinically meaningful separation of pridopidine at all timepoints and for key outcome measures. PROOF-HD is the first trial to demonstrate benefit on multiple clinical measures of disease progression in HD.

Authors/Disclosures
Michael Hayden PRESENTER	No disclosure on file
Michal Geva (Prilenia Therapeutics)	No disclosure on file
Ralf Reilmann, MD, FAAN (George-Huntington-Institute)	The institution of Dr. Reilmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. The institution of Dr. Reilmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for uniQure. The institution of Dr. Reilmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for WAVE. Dr. Reilmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for WAVE. The institution of Dr. Reilmann has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for IOS-Press. The institution of Dr. Reilmann has received research support from European Union. Dr. Reilmann has a non-compensated relationship as a Executive Committee Member with Huntington Study Group that is relevant to AAN interests or activities. Dr. Reilmann has a non-compensated relationship as a Member of Executive Committee with European Huntington Disease Network that is relevant to AAN interests or activities. Dr. Reilmann has a non-compensated relationship as a Co-Chair Task Force on Huntington Disease with Movement Disorders Socitey that is relevant to AAN interests or activities.
Andrew S. Feigin, MD (NYU Langone Health)	Dr. Feigin has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ADCS/ATRI. Dr. Feigin has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC. Dr. Feigin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Feigin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aspen. Dr. Feigin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AskBio. Dr. Feigin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Feigin has received research support from Huntngton Study Group. The institution of Dr. Feigin has received research support from Prilenia.
Anne Rosser	No disclosure on file
Sandra K. Kostyk, MD, PhD (Prilenia Therapeutics.)	Dr. Kostyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WaveLifeScience. Dr. Kostyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Kostyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Kostyk has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Prilenia Therapeutics. The institution of Dr. Kostyk has received research support from Michael J Fox Foundation. The institution of Dr. Kostyk has received research support from Craig Nielsen Foundation. The institution of Dr. Kostyk has received research support from CHDI Foundaton. The institution of Dr. Kostyk has received research support from UniQure. The institution of Dr. Kostyk has received research support from Voyager Therapeutics. The institution of Dr. Kostyk has received research support from WaveLife Sciences. The institution of Dr. Kostyk has received research support from Vaccinex . The institution of Dr. Kostyk has received research support from Neurocrine Biosciences. The institution of Dr. Kostyk has received research support from Prilenia.
Kelly Chen	No disclosure on file
Munish Mehra	No disclosure on file
Yael Cohen	Yael Cohen has nothing to disclose.
Paul Goldberg	Paul Goldberg has received personal compensation for serving as an employee of Prilenia. Paul Goldberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Ionis Pharmaceuticals. Paul Goldberg has stock in Prilenia.