Nature Medicine Publishes Phase 3 Data on Pridopidine, Offering Hope in Early-Stage Huntington’s Disease
Prilenia Therapeutics B.V., a clinical-stage biopharmaceutical company specializing in neurodegenerative diseases, together with its partner Ferrer, announced a significant milestone in the scientific and medical understanding of Huntington’s disease (HD). The journal Nature Medicine, one of the world’s leading peer-reviewed publications, released a full manuscript detailing results from a Phase 3 clinical trial evaluating pridopidine, a first-in-class oral sigma-1 receptor (S1R) agonist.
The study, titled “Pridopidine in Early-Stage Manifest Huntington Disease: A Phase 3 Trial”, focuses on early-stage HD patients and delivers encouraging results: pridopidine demonstrated the ability to slow clinical progression in patients not receiving antidopaminergic medicines (ADMs). This finding, based on data from the PROOF-HD trial, could represent a turning point for the HD community, where no disease-modifying treatments currently exist.
For families and patients facing this devastating disease, the publication is more than a scientific achievement—it is a source of renewed hope that the trajectory of HD progression can be altered.
Key Findings from the PROOF-HD Phase 3 Trial
Trial Overview
The PROOF-HD study was designed to assess whether pridopidine could influence disease progression in patients with early-stage Huntington’s disease. While the overall trial population did not meet the primary endpoint, pre-defined analyses of subgroups uncovered a striking finding: patients not taking ADMs—commonly used to manage chorea and other symptoms—experienced clinically meaningful benefits across multiple domains.
Clinical Outcomes Measured by cUHDRS
The main tool used to measure disease progression was the composite Unified Huntington’s Disease Rating Scale (cUHDRS). This scale integrates assessments of function, cognition, and motor skills, providing a comprehensive view of patient status over time.
In the subgroup of patients not on ADMs, pridopidine showed consistent improvements:
- At 26 weeks: change vs placebo of 0.46
- At 39 weeks: change vs placebo of 0.45
- At 52 weeks: change vs placebo of 0.41
- At 65 weeks (end of trial): change vs placebo of 0.27
To contextualize these results, prior studies indicate that annual reductions of just 0.1–0.3 points in cUHDRS correlate with clinically meaningful benefits. The values observed in the trial suggest that pridopidine meaningfully slowed disease progression over the study duration.
Broader Impact Across Clinical Domains
Importantly, the Nature Medicine benefits extended beyond cUHDRS. Patients maintained cognitive function and motor performance, outcomes measured by two well-established tools:
- Stroop Word Reading Test (SWR): Evaluated cognitive function and showed no deterioration in the pridopidine group.
- Quantitative Motor (Q-Motor): Assessed fine motor skills, again showing maintenance rather than decline.
Together, these measures reinforce pridopidine’s potential to preserve essential abilities that underpin daily living.
Expert Perspectives on the Findings
The publication was accompanied by commentary from clinicians, researchers, patient advocates, and company leadership.
Dr. Ralf Reilmann: Clinical Significance and Safety Profile
Dr. Ralf Reilmann, MD, FAAN, Founding Director of the George Huntington Institute and lead author of the publication, emphasized the novelty of the findings.
“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 Nature Medicine confirming pridopidine’s favorable safety and tolerability profile.”
He also noted that future studies must refine patient selection, particularly accounting for ADM exposure, which may have masked the true therapeutic effect in the broader population. Stratifying patients by medication use will allow future trials to more clearly demonstrate pridopidine’s benefits.
Patient Advocate Perspective: Hope for Families
For the Huntington’s disease community, the trial represents more than data—it represents possibility. Nature Medicine Dina de Sousa, a Board member of the European Huntington Association (EHA), captured this sentiment:
“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.”
Her words highlight the profound unmet need: families affected by HD have long lived without any Nature Medicine therapy that changes disease progression.
Company Leadership: Roadmap for the Future
Prilenia’s CEO, Dr. Michael R. Hayden, underscored the forward-looking implications of the trial:
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.”
Ferrer’s Chief Scientific Officer, Oscar Pérez, placed the findings in a broader scientific and therapeutic context:
“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 Nature Medicine approach and the development of pridopidine for the treatment of neurodegenerative diseases such as HD and ALS.”
Together, these Nature Medicine perspectives reflect a coordinated push: advancing toward regulatory approval while reinforcing scientific credibility.
About Pridopidine: Mechanism and Development Path
What Is Pridopidine?
Pridopidine is a potent, selective sigma-1 receptor (S1R) agonist taken orally at a dosage of 45 mg twice daily. The sigma-1 receptor plays a critical role in cellular survival pathways, particularly in conditions of stress. In neurodegenerative diseases such as Huntington’s disease and amyotrophic lateral sclerosis (ALS), the receptor’s activity is impaired.
By stimulating the S1R, pridopidine is thought to activate neuroprotective mechanisms, improving neuronal resilience and function. This Nature Medicine mechanism differs fundamentally from currently available HD therapies, which focus exclusively on symptomatic relief rather than modifying the underlying disease trajectory.
Safety and Tolerability Profile
Pridopidine has been studied in approximately 1,600 individuals across multiple trials. The accumulated evidence Nature Medicine demonstrates a favorable safety profile, with most adverse events being mild to moderate and comparable to placebo.
This tolerability is particularly important in HD, where patients already contend with multiple medications and often face barriers to adherence.
Development Beyond Huntington’s Disease
While the publication focuses on HD, pridopidine’s development extends to ALS. Building on encouraging signals from the Phase 2 HEALEY ALS Platform Trial, Prilenia and Ferrer plan to initiate a pivotal Phase 3 trial in ALS in early 2026. This program will focus on patients with early and rapidly progressing disease.
The drug has received Orphan Drug designation in both HD and ALS in the United States and the European Union, along with FDA Fast Track designation for HD. These regulatory designations are intended to accelerate the development of therapies for rare, serious conditions with high unmet need.
Understanding Huntington’s Diseas
A Genetic, Progressive Disorder
Huntington’s disease is a rare, inherited neurodegenerative condition caused by a mutation in the huntingtin gene. Nature Medicine It follows an autosomal dominant inheritance pattern, meaning each child of an affected parent has a 50% chance of developing the disease.
Globally, HD affects approximately 4.88 per 100,000 people, with an estimated 300,000 individuals at risk.
Symptoms and Progression
HD typically begins between ages 30 and 50 but can occur earlier (juvenile-onset HD). The disease is characterized by a relentless decline in multiple domains:
- Motor Symptoms: Chorea (involuntary movements), impaired coordination, and difficulties with balance.
- Cognitive Symptoms: Declines in executive function, memory, and attention.
- Behavioral Symptoms: Depression, irritability, and other psychiatric manifestations.
Over 15 to 20 years, patients progressively lose independence, becoming fully reliant on caregivers. The Nature Medicine disease ultimately leads to premature death.
Current Treatment Landscape
Currently approved therapies for HD focus exclusively on symptom management, primarily targeting chorea and psychiatric symptoms. Nature Medicine These treatments do not slow or halt disease progression. For patients and families, this reality creates a deep unmet medical need—making the results with pridopidine particularly noteworthy.
About Prileni
Prilenia Therapeutics is a private biopharmaceutical company headquartered in the Netherlands. The Nature Medicine company is dedicated to developing transformative therapies for neurodegenerative diseases, with a focus on HD and ALS.
Key attributes of Prilenia include:
- Retention of commercialization rights for pridopidine in North America, Japan, and Asia Pacific.
- A strong commitment to scientific rigor and patient-centered development.
- Backing from leading life sciences investors.
About Ferre
Founded in Barcelona in 1959, Ferrer is a global pharmaceutical company with operations in more than 100 countries. What sets Ferrer apart is its corporate philosophy: the Nature Medicine company prioritizes reinvesting profits into social initiatives, sustainability, and ethical practices rather than maximizing shareholder returns.
- In 2022, Ferrer became a certified B Corp, reflecting its commitment to social responsibility.
- The company focuses on transformative solutions in pulmonary vascular diseases, interstitial lung diseases, and rare neurological disorders.
- With 1,800 employees worldwide, Ferrer operates with the belief that business is not an end in itself but a means to create positive societal change.
A Step Toward Disease Modification in HD
The publication of pridopidine’s Phase 3 trial results in Nature Medicine represents a critical milestone in Huntington’s disease research. While not definitive, the evidence from the ADM-free subgroup provides a strong signal that pridopidine can slow disease progression across multiple domains.
For the HD community, which has long endured without a disease-modifying therapy, these findings bring renewed hope. They also establish a clear roadmap: a global confirmatory trial beginning next year, ongoing regulatory engagement, and continued exploration of pridopidine in ALS.
The road ahead will demand rigorous science, careful patient selection, and transparent collaboration between companies, clinicians, and patient advocates. But for the first time in decades, there is a tangible possibility that the course of Huntington’s disease can be altered—not just managed.
