Nature Medicine Publishes Phase 3 Data on Pridopidine in Early-Stage Huntington’s Disease, Highlighting Impact on Clinical Progression
NAARDEN, The Netherlands and WALTHAM, Mass. / BARCELONA, Spain, 05 September 2025 --- Prilenia Therapeutics B.V. and Ferrer today announced the publication, in the journal Nature Medicine, of a manuscript entitled "Pridopidine in Early-Stage Manifest Huntington Disease: A Phase 3 Trial" . The publication describes data showing that treatment with pridopidine slowed clinical progression in Huntington’s disease (HD) patients not taking antidopaminergic medicines (ADMs).
The published data, from pre-defined analyses of a subgroup of patients not taking ADMs from pridopidine’s Phase 3 PROOF-HD trial, show that treatment with pridopidine achieved a clinically meaningful improvement from baseline for one year and slowing of decline thereafter, as measured by cUHDRS, with change vs placebo of ¬0.46, ¬0.45, ¬0.41 and ¬0.27 at 26, 39, 52 and 65 weeks (the end of the double-blind trial). Annual reductions in cUHDRS of 0.1–0.3 points have been associated with a clinically meaningful benefit in HD.
Importantly, the benefits in cUHDRS in this subgroup of subjects with HD were seen across domains of function, cognition, and motor performance. Pridopidine also achieved similar maintenance of cognition with no deterioration, as measured by Stroop Word Reading Test (SWR), and motor performance, as measured by Quantitative Motor (Q-Motor).
Ralf Reilmann, MD, FAAN, Founding Director, George Huntington Institute and publication lead author, said: “The published data represents the first Phase 3 HD trial to deliver consistent and meaningful benefits on progression across multiple clinical domains of HD such as function, cognition and motor performance, while also confirming pridopidine’s favorable safety and tolerability profile. Upcoming studies can now refine patient selection and account for the impact of ADM exposure, which obscured the true drug-related benefits. Appropriate stratification and dosage strategies will control for this confounding factor and allow demonstration of pridopidine’s positive treatment effects on clinical progression of symptoms. I would like to express my gratitude for the continued commitment of everyone working to support the next data-driven steps to making this well-tolerated and easily administered treatment option available to HD patients.”
Dina de Sousa, European Huntington Association (EHA) Board member, remarked: “We have no options to help slow down our decline. Nothing to help people feed themselves a little longer, button a shirt a little longer, walk a little longer, or maybe even dance a little longer. Treatment options are needed now that can enable maintenance of independence for as long as possible. These results provide hope that there are therapies that can go further than just symptom control, and hope that we can take a step forward toward availability of a disease-modifying treatment able to slow down the inexorable march of this dreadful disease.”
“These data provide a clear path forward for next year’s planned global confirmatory study in early HD patients, aimed at confirming pridopidine’s effect and supporting ongoing global regulatory discussions,” said Dr. Michael R. Hayden, CEO of Prilenia.
“Nature Medicine is one of the world’s leading peer-reviewed medical journals, and this important publication adds to the weight of evidence in support of the sigma-1 receptor agonist approach and the development of pridopidine for the treatment of neurodegenerative diseases such as HD and ALS,” said Oscar Pérez, Chief Scientific Officer at Ferrer.
About pridopidine
Pridopidine (45 mg twice daily) is a potent and selective, orally administered sigma-1 receptor (S1R) agonist which stimulates key neuroprotective mechanisms impaired in neurodegenerative diseases such as HD and ALS.
Pridopidine’s extensive development program involved approximately 1,600 people, demonstrating a favorable safety and tolerability profile.
In addition to HD, pridopidine is in late-stage clinical development for ALS, with Prilenia and Ferrer planning to initiate a single, pivotal Phase 3 trial in ALS early in 2026, building on the findings in the population with early and rapid progressing disease from the Phase 2 HEALEY ALS Platform Trial.
Pridopidine has Orphan Drug designation in HD and ALS in the US and EU, and FDA Fast Track designation for the treatment of HD .
About Huntington’s Disease
Huntington’s disease (HD) is a rare, inherited, autosomal dominant, neurodegenerative disease that results in functional, motor, cognitive and behavioral symptoms. HD is caused by a mutation in the huntingtin gene , and each child of a parent with HD has a 50 percent chance of developing the disease.
HD affects approximately 4.88 out of 100,000 people around the world with an additional 300,000 people at risk of developing HD. It is usually diagnosed between the ages of 30 and 50, although HD can occur at any age, including in children and young adults (known as juvenile onset HD or JHD). The disease progresses slowly over 15 to 20 years, with patients slowly losing their ability to work, communicate, manage day-to-day life and take care of themselves. This increasing disability leads to full reliance on a caregiver and, ultimately, death.
The only currently available treatments for HD focus on symptomatic relief and palliative care, with nothing impacting measures of overall progression.