Pridopidine Hits a Roadblock: EMA Says No to Approval for Huntington’s Disease Treatment

We learned on July 25, 2025 that Prilenia’s application to the European Medicines Agency’s (EMA) for pridopidine was not accepted for marketing authorization. While this is perhaps not surprising given the data around this drug in clinical trials thus far, it still comes as a great disappointment for the HD community. So what does this mean for the future of pridopidine? Let’s discuss. 

What is Pridopidine?

Pridopidine (previously called huntexil) is an experimental oral drug being developed primarily for Huntington’s disease (HD), and now also for ALS. It was originally thought to act by influencing dopamine signalling with the hope of improving movement symptoms for people with HD.

However, continued scientific research suggested that its effects seem to be mediated by activation of the sigma‑1 receptor (S1R), a protein found in nerve cells that helps manage cellular stress to maintain healthy cellular function. 

Pridopidine Clinical Trials

Multiple trials including HART, MermaiHD, and PRIDE‑HD found that while pridopidine was safe and well tolerated, it failed to meet its primary motor endpoints. Yet post‑hoc analyses, which is a way to examine data after the trial is run, suggested there might have been possible benefits in Total Functional Capacity (TFC) in some people with HD. TFC scores measure how well people can function at tasks like managing their households and finances, ability to work, drive, cook, and do other day-to-day activities. 

Pridopidine works through activation of the sigma‑1 receptor (S1R), a protein found in nerve cells that helps manage cellular stress to maintain healthy cellular function. 

That possibility of a benefit in TFC led to the Phase 3 PROOF‑HD trial focusing on function rather than motor symptoms. Post hoc analyses, like this one which pointed to TFC, are generally not sufficient for drug approval but can give insight into a subgroup of people or a dosage where the drug might be working. 

So while PROOF‑HD did not meet its pre‑specified primary endpoints in the overall population, exploratory subgroup analyses (especially excluding participants on dopamine‐altering medications) showed there may have been some favorable signals on function, cognition, and motor measures, though those results remain inconclusive.

Applying for EMA Marketing

Based on these potential favorable data in a subset of people with HD not on certain medications, Prilienia applied to the EMA for marketing approval in September of 2024. 

This application involved putting together a massive dossier of information that contained all the previous data around pridopidine. If it was approved, that would mean Prilenia would have the right to sell pridopidine in Europe for the treatment of HD. If it was rejected, that would send Prilenia back to the drawing board. 

After Prilenia submitted their application to the EMA, they announced a partnership with Ferrer, a Spanish pharmaceutical company. Their partnership was intended to further develop and commercialize pridopidine.  

So where do we stand?

July 2025 Update

In their most recent update, Prilenia and Ferrer shared that the EMA refused authorization for pridopidine’s marketing authorization application for HD. This means pridopidine will not be sold for the treatment of HD in Europe. 

Despite what will undoubtedly come as a disappointment for many in the HD community, Prilenia and Ferrer emphasized their continued commitment to advancing pridopidine for the HD and ALS communities. In their statement, they said their plan is to initiate a “potentially registrational global HD study” in the near term. 

So it appears that while Prilenia and Ferrer have been dealt a setback, they don’t have plans to discontinue advancing pridopidine for HD. Like you, we’ll have to wait to hear more from these companies about their specific plans. 

Looking Forward

The failure of advancement for any HD drug is a massive disappointment. However, the data around pridopidine suggested this was the likely outcome, at least for now. While we did our best to temper expectations within the community, we understand that many HD families were still holding onto hope. That hope is never misplaced; it’s what drives the entire research effort forward.

At HDBuzz, our job is to share not just the excitement, but also the realities based on the best available science. We don’t take lightly the responsibility of being your trusted source, and we’ll continue to bring you the clearest, most objective updates possible — no hype, no false hope, just real science.

In their most recent update, Prilenia and Ferrer shared that the EMA refused authorization for pridopidine’s marketing authorization application for HD. This means pridopidine will not be sold for the treatment of HD in Europe.

Even with setbacks like this one, 2025 has already been a remarkable year for HD research with positive updates from uniQure and PTC Therapeutics, a trial from Skyhawk Therapeutics advancing, and the first doses being given in Phase 1 trials by Spark Therapeutics and Alnylam. And there’s still more news expected to come! 

Promising trials, innovative approaches, and new insights are on the horizon, all pushed forward by you, the HD community. So don’t give up hope, because the path to progress is rarely straight, but it is still moving forward. And we’ll be here to walk it with you, every step of the way.

TL;DR

The European Medicines Agency (EMA) has rejected Prilenia’s application to approve pridopidine for treating Huntington’s disease (HD) in Europe.

Although safe and well-tolerated, pridopidine failed to meet primary endpoints in several trials, including the Phase 3 PROOF-HD study, though some exploratory subgroup data showed modest signals.

Despite the setback, Prilenia and Ferrer remain committed to developing pridopidine.

Learn more

Original press release (open access).