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16 December  |  2020

Additional analyses of Efficacy and Safety of Pridopidine for Huntington’s Disease demonstrate positive effect on functional capacity

  • Positive results from additional analyses of PRIDE-HD and Open-HART trials with pridopidine published in peer-reviewed journal, The Journal of Huntington’s Disease.

  • Exploratory additional efficacy data show pridopidine (45 mg bid) to be the first drug to exert a significant and clinically meaningful beneficial effect on Total Functional Capacity (TFC).

  • Results from Open-HART trial demonstrate potential durability of the effect of pridopidine with less TFC decline over 5 years compared to historical placebo group, as well as positive safety and tolerability data.



[Naarden, NL, 16 December 2020]  Prilenia Therapeutics B.V., a clinical stage biotech company focused on developing novel treatments for neurodegenerative and neurodevelopmental disorders, today announces the publication of two articles in the peer-reviewed journal, The Journal of Huntington’s Disease, highlighting positive efficacy and safety data for pridopidine, as demonstrated by new additional analyses of the Phase 2 PRIDE-HD and Open-HART trials. 
Pridopidine is a first-in-class small molecule in development for the treatment of Huntington’s disease (HD) and Amyotrophic Lateral Sclerosis (ALS). It is the most selective, high-affinity Sigma-1-receptor (S1R) agonist in clinical development. Activation of the S1R by pridopidine exerts neuroprotective effects in preclinical models of HD and other in neurodegenerative diseases. 

Highlights from the published articles include the following: 

1. Effects of Pridopidine on Functional Capacity in Early-Stage Participants from the PRIDE-HD Study

  • Pridopidine 45 mg bid is the first drug to demonstrate a beneficial effect on TFC at 52 weeks in HD patients (∆TFC vs placebo 0.87, p=0.0032). The effect was more pronounced in early-stage HD patients (∆TFC vs placebo 1.16, p=0.0003).

  • The effect remains nominally significant using the most conservative, worst-case scenario Missing Not at Random (MNAR) sensitivity analysis.

  • Responder analysis demonstrates that treatment with pridopidine 45 mg bid reduces the probability to decline in TFC by approximately 80%.

2. Additional Safety and Exploratory Efficacy Data at 48 and 60 Months from Open-HART, an Open-Label Extension Study of
     Pridopidine in Huntington Disease


  • Pridopidine 45 mg bid demonstrates a durable effect on slowing the decline in TFC versus a historical placebo group over 5 years. Pridopidine remained safe and tolerable over 60 months.

  • Early HD patients treated with pridopidine 45 mg bid show less decline in TFC at 60 months (-1.8 points/5 years) compared to historical placebo group demonstrating the expected decline in TFC (-5.0/5 years) (nominal p<0.001).

  • This effect remains nominally significant after sensitivity analysis with mixed model repeated measures to account for missing data.

Andrew McGarry, MD, Director, Clinical Development, Clintrex and lead author of the PRIDE-HD and Open-HART publications, commented: “Pridopidine has demonstrated an excellent long-term safety profile and suggestion of improvement in clinical trials, as well as in exploratory analyses, where early HD populations appear to particularly benefit. In view of these promising data, the newly initiated Phase 3 study in HD will be of great interest to the entire HD community."  

Pridopidine is an orally administered drug currently being assessed in a Phase 3 randomized, double-blind, placebo-controlled study (PROOF-HD), evaluating the effect of pridopidine 45 mg bid on Total Functional Capacity (TFC) in patients with early stage HD. The first patients in this trial were dosed in October 2020.  TFC is the standard widely used clinical scale for tracking the progression of HD with respect to functional capacity. In addition, TFC is accepted by the FDA and EMA as a single primary endpoint in HD trials. Pridopidine is also being assessed in the first ever platform trial for ALS in collaboration with the Healey Center for ALS at Mass General Hospital.

Ralf Reilmann, MD, Founding Director of the George Huntington Institute and Principal Investigator of the PROOF-HD Phase 3 clinical trial in Europe, commented: “These are critical results. At the 45 mg bid dosage used in the Phase 2 Pride-HD and Open-HART trials, pridopidine is the first drug to show a significant clinical effect on the functional decline caused by Huntington’s disease progression, as well as long-term safety data. The PROOF-HD Phase 3 trial will be an important next step to see if pridopidine can offer an effective and safe treatment that allows patients to better maintain their functional and motor abilities, and quality of life.”

Michael R. Hayden, MD, PhD, CEO of Prilenia and world-renowned expert in Huntington’s Disease research, commented: “Pridopidine is showing strong scientific and clinical data in support of its use for Huntington’s disease and other neurodegenerative diseases, such as ALS. By understanding the mechanism of action clearly, we are now delighted about the reported positive data in terms of efficacy and safety.”

Pridopidine is a first in class small molecule developed by Prilenia for the treatment of neurodegenerative disorders such as HD and Amyotrophic Lateral Sclerosis (ALS). Pridopidine is a highly selective Sigma-1 receptor (S1R) agonist. It binds and activates the S1R, a protein that is expressed at high levels within the brain and regulates key cellular pathways, commonly impaired in neurodegeneration. 

Further details of the ongoing PROOF-HD trial can be found here:

For further information, please contact:

Prilenia Therapeutics

Michael Hayden, CEO
Limor Ben Har, COO

Instinctif Partners
Melanie Toyne-Sewell / Agnes Stephens / Siobhan Sanford
T: +44 (0) 207 457 2020



Notes to Editors

About Pridopidine


Prilenia’s lead asset is Pridopidine, a first-in-class drug candidate with an established safety profile and therapeutic potential in several neurodegenerative diseases affecting adults and children. The highly selective S1R agonist was acquired from Teva in 2018.


Pridopidine’s favorable safety profile has been established in clinical trials in >1300 study participants, exposed to various doses for a total of ~1300 patient years.

Pridopidine for Huntington's Disease


HD is a fatal, inherited, neurodegenerative disorder. Every offspring of an HD patient has a 50% chance of inheriting the gene. Usually starting at around 40 years of age, HD patients suffer from movement disorder, progressive functional and cognitive decline, psychiatric disturbances and behavioral symptoms. Following diagnosis, functional, motor and cognitive functions decline steadily, ultimately leading to immobility, dementia and premature death.


Pridopidine has demonstrated maintenance of functional capacity in HD patients, as measured by Total Functional Capacity (TFC), in a clinical trial. This effect was most prominent in early stage HD patients (HD1 and HD2), who showed functional benefit from pridopidine 45 mg, taken twice a day.


There is extensive preclinical evidence that further supports pridopidine’s potential beneficial effect in HD. The therapeutic effect has been shown to be mediated exquisitely by the sigma-1 receptor (S1R) using multiple deletion and antagonist models.


Prilenia has an orphan drug designation for pridopidine for the treatment of HD in both the US and Europe.


PROOF-HD is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of pridopidine in patients with early stage of Huntington’s Disease. The purpose of the study is to evaluate the effect of pridopidine 45mg bid on functional capacity, as well as on motor and behavioral features. 


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