EMA Turns Down Nurzigma for Huntington Disease

At its July 2025 meeting, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended against granting marketing authorization in the European Union for Nurzigma (pridopidine, Prilenia Therapeutics) for treating adults with Huntington disease. 

Huntington disease is a rare, inherited, and fatal neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms. It affects approximately 5-10 individuals per 100,000 in the European population, which translates to an estimated 25,000-50,000 cases across the European Union. However, it currently lacks approved therapies to slow its progression. The available treatments only offer limited symptom control for Huntington disease-related complications, including chorea and behavioral issues.

The active substance in Nurzigma, pridopidine, functions as an agonist of the sigma-1 receptor (S1R) within cellular structures, modulating pathways crucial for neuronal health and viability. This action on S1R is thought to ameliorate cellular dysfunctions associated with neuronal injury and Huntington disease, facilitating neurogenesis and attenuating oxidative stress, slowing neurodegenerative processes. 

Primary Endpoints Unmet in Trials

Multiple clinical trials — including HART, MermaiHD, and PRIDE-HD — showed that, while pridopidine was generally safe and well tolerated, it failed to meet its primary motor endpoints. Despite this, post-hoc analyses suggested potential benefits in total functional capacity (TFC) in some patients. TFC scores assess how well individuals can perform day-to-day activities, including managing household tasks, finances, work, driving, and cooking.

These findings led to the phase 3 PROOF-HD trial, which focused on functional outcomes rather than motor symptoms. However, the trial did not meet its primary endpoint, which was the change in TFC, in the overall study population. Post-hoc subgroup analyses showed potential benefits, particularly in patients not taking antidopaminergic medications. While these findings offered some insights into potential drug efficacy, the CHMP found them insufficiently robust and lacking in external validity.

Despite setbacks, Prilenia Therapeutics and Ferrer said they are committed to advancing Nurzigma for Huntington disease, with new global studies planned to confirm its effectiveness. The companies have confirmed that the EMA’s negative opinion on Nurzigma has no impact on patients currently enrolled in clinical trials or receiving the drug through compassionate use programs. Ongoing access and treatment protocols remain unchanged. However, patients should consult their clinical trial investigators for specific information regarding their continued treatment.