NAARDEN (Netherlands) and WALTHAM (USA) / BARCELONA (Spain), September 5, 2025- Prilenia Therapeutics B.V. and Ferrer announce the publication in the journal Nature Medicine of the article "Pridopidine in Early-Stage Manifest Huntington Disease: A Phase 3 Trial". The publication describes data showing that pridopidine treatment slowed clinical progression in patients with Huntington's disease (HD) who were not taking antidopaminergic drugs (ADMs).
The published data, from predefined analyses of a subgroup of patients in the Phase 3 PROOF-HD trial, show that pridopidine achieved clinically meaningful improvement from baseline for one year and a slowing of subsequent deterioration, as measured with cUHDRS, with a difference versus placebo of 0.46, 0.45, 0.41, and 0.27 at 26 weeks, 39, 52 and 56 (the end of the double-blind clinical trial). Annual reductions in cUHDRS of 0.1 to 0.3 points have been associated with a clinically significant benefit in HD.
Notably, the benefits in cUHDRS in this subgroup were observed in the domains of function, cognition, and motor function. Pridopidine also showed similar maintenance of cognition (Stroop Word Reading test, SWR) and motor performance (Q-Motor). The data also confirmed that the treatment was well tolerated, with a favorable safety profile.
Ralf Reilmann, MD, FAAN, Founding Director of the George Huntington Institute and lead author of the publication, notes: "The published data represent the first phase 3 trial in Huntington's disease to demonstrate consistent and significant benefits on progression across multiple clinical domains of the disease, such as function, cognition and motor function, while confirming the favourable safety and tolerability profile of pridopidine. Upcoming studies will be able to refine patient selection and take into account the impact of exposure to ADMs, which masked the true benefits related to the drug. Adequate stratification and dosing strategies will allow this confounding factor to be controlled and the positive effects of pridopidine on the clinical progression of symptoms to be demonstrated. I appreciate the continued commitment of all working to support the next steps, guided by the data, towards the availability of this well-tolerated and easily administered treatment option for patients with Huntington's disease."
Dina de Sousa, a member of the Board of the European Huntington Association (EHA), adds: "We have no options to help slow our deterioration. Nothing that allows people to feed themselves for a little longer, button a shirt for a little longer, walk for a little longer, or even dance for a little longer. Treatments are needed to help maintain independence for as long as possible. These results give us hope that there may be therapies that go beyond symptom control, and take a step towards the availability of a disease-modifying treatment capable of slowing its inexorable progression."
"These data mark a clear path toward the global confirmatory study planned for next year in patients with early-stage Huntington's disease, with the goal of confirming the effect of pridopidine and supporting ongoing regulatory discussions," said Michael R. Hayden, M.D., CEO of Prilenia.
"Nature Medicine is one of the leading peer-reviewed medical journals in the world, and this publication adds weight to the evidence supporting the sigma-1 receptor agonist approach and the development of pridopidine for the treatment of neurodegenerative diseases such as Huntington's disease and ALS," said Oscar Perez, Ph.D. Chief Scientific Officer of Ferrer.
About Pridopidine
Pridopidine (45 mg twice daily) administered orally, is a potent and selective agonist of the sigma-1 receptor (S1R), which stimulates key neuroprotective mechanisms in neurodegenerative diseases such as HD and ALS. The clinical development program of pridopidine has involved approximately 1,600 people, demonstrating a favorable safety and tolerability profile.
In addition to HD, pridopidine is in late clinical development for ALS. Prilenia and Ferrer plan to initiate a pivotal Phase 3 trial in ALS in early 2026, based on findings obtained in the early-stage and rapidly progressing population of the Phase 2 HEALEY ALS Platform Trial.
Pridopidine has orphan drug designation for HD and ALS in both the US and EU, as well as FDA Fast Track designation for the treatment of HD.
About Huntington's disease
Huntington's disease (HD) is a rare, hereditary, autosomal dominant and neurodegenerative disease, which causes functional, motor, cognitive and behavioural symptoms. It is caused by a mutation in the huntingtin gene and each child of a parent with HD has a 50% chance of inheriting the disease.
HD affects approximately 4.88 out of every 100,000 people worldwide, with about 300,000 more people at risk of developing it. It is usually diagnosed between the ages of 30 and 50, although it can appear at any age, including children and young people (known as juvenile HD or JHD). The disease progresses slowly over 15 to 20 years, with a gradual loss of the ability to work, communicate, perform daily activities, and care for oneself autonomously, leading to total dependence on a caregiver and eventually death.
Currently available treatments for HD focus on symptomatic relief and palliative care, without affecting the overall progression of the disease.
