Neuren Pharmaceuticals (ASX: NEU) has confirmed its partner Acadia Pharmaceuticals will request a formal re-examination of the European regulator’s negative opinion on trofinetide for Rett syndrome treatment. The Neuren trofinetide CHMP re-examination follows a formal vote by the Committee for Medicinal Products for Human Use (CHMP) confirming the earlier trend vote recommending refusal of marketing authorisation for patients 2 years of age and older.
Trofinetide is approved in the United States, Canada, and Israel as the first and only treatment for Rett syndrome, where it has been commercially available for nearly 3 years. Neuren, the originator of trofinetide, receives royalties from partner Acadia under an exclusive worldwide licensing agreement.
Acadia to challenge European regulator decision on trofinetide
Acadia Pharmaceuticals confirmed it plans to request re-examination of the CHMP opinion regarding the Marketing Authorisation Application for trofinetide. The formal CHMP vote confirmed the previously announced trend vote recommending refusal.
The drug has demonstrated commercial success in approved markets. In the United States, trofinetide is marketed as DAYBUE® oral solution and DAYBUE STIX powder, both approved by the US Food and Drug Administration. Health Canada and Israel’s Ministry of Health have also granted approval for the oral solution formulation.
Acadia CEO Catherine Owen Adams stated the company remains committed to working constructively with EU regulators. “While we are disappointed by the CHMP’s recommendation to refuse approval, we continue to be encouraged by the meaningful benefits trofinetide has demonstrated for people living with Rett syndrome,” she said. The strong engagement from patients, caregivers, and clinicians reinforces the company’s belief in the treatment’s clinical value.
The re-examination pathway keeps the European market opportunity open for a therapy already generating commercial revenue in three approved jurisdictions.
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What is the CHMP re-examination process?
The Committee for Medicinal Products for Human Use (CHMP) is the scientific committee of the European Medicines Agency responsible for evaluating medicines for use in the European Union. When an applicant receives a negative opinion, they have the right to request a second review of their application.
The re-examination process involves several key steps:
- The applicant submits a formal request for re-examination within 15 days of receiving the negative opinion
- The EMA assigns a new rapporteur panel to reassess the application
- The applicant can provide new arguments, clarifications, or additional data to address the concerns raised
- The new panel conducts a fresh evaluation of the evidence
- A final opinion is issued, typically within approximately 60 days from request acceptance
This is a standard regulatory pathway built into the European medicines approval system, not an appeal to a judicial body. The re-examination offers applicants an opportunity to address specific concerns raised by the initial review committee.
Understanding this process helps investors assess realistic timelines for a potential European approval decision. The 60-day timeframe provides clarity on when a final outcome might be expected once the re-examination is formally accepted.
CHMP concerns and Acadia’s response strategy
The CHMP issued its refusal despite the pivotal LAVENDER clinical trial successfully meeting its co-primary and key secondary endpoints. The committee cited three main concerns that influenced its decision.
| CHMP Concern | Clinical Trial Context |
|---|---|
| Treatment effect magnitude after 12 weeks viewed as limited | Trial met co-primary and key secondary endpoints |
| Study did not capture all core symptoms of Rett syndrome | Study designed around validated Rett syndrome assessment tools |
| Long-term outcome assessment affected by patient discontinuations | Common challenge in rare paediatric disease trials |
The 12-week treatment period assessed in the trial produced measurable effects, though the CHMP considered the magnitude limited. The committee also noted that assessment of longer-term outcomes was influenced by patient discontinuations over time, a recognised challenge in rare paediatric disease studies.
Acadia stated this feedback provides important information as it considers the intended re-examination. The specific nature of the concerns suggests they may be addressable through additional data presentation or clarification rather than requiring new clinical trials, which would represent a far longer pathway.
The fact that trofinetide has demonstrated real-world effectiveness in three approved markets over nearly 3 years may provide supportive evidence during the re-examination process.
Management commentary
Jon Pilcher, CEO of Neuren, expressed full support for the re-examination process and highlighted the urgent medical need in Europe:
Jon Pilcher, CEO
“Neuren fully supports a re-examination of the CHMP opinion. Trofinetide has been making a difference for patients for nearly three years in approved markets and the unmet medical need in Europe remains substantial and urgent.”
The statement from Markus Schulze, a caregiver and member of the Rett Syndrome Society Nordrhein-Westfalen from Germany, underscored the patient community perspective. “Our family and others who play an important role in the delivery of care know first-hand the challenges that individuals living with Rett syndrome face every day. It is our hope that this important therapy will be approved to help the EU Rett community better navigate life with Rett syndrome,” he said.
Neuren’s broader pipeline and commercial position
Neuren Pharmaceuticals has granted an exclusive worldwide licence to Acadia Pharmaceuticals for the development and commercialisation of trofinetide. Under this arrangement, Neuren receives royalties from sales in approved markets, providing ongoing revenue independent of the European outcome.
The company’s pipeline extends beyond trofinetide. Neuren’s second drug candidate, NNZ-2591, is currently in Phase 3 development. The company is conducting a randomised, double-blind, placebo-controlled clinical trial called Koala, evaluating the safety and efficacy of NNZ-2591 in children aged 3 to 12 years with Phelan-McDermid syndrome, alongside a 52-week open-label extension study.
NNZ-2591 is being developed as an oral solution treatment for multiple neurodevelopmental disorders:
- Phelan-McDermid syndrome (currently in Phase 3)
- Pitt Hopkins syndrome (positive Phase 2 results achieved)
- Angelman syndrome (positive Phase 2 results achieved)
- Hypoxic ischaemic encephalopathy (HIE), a condition caused by brain injury before or shortly after birth
The regulatory pathway for NNZ-2591 has received significant support:
- Orphan drug designation in the United States and European Union for multiple indications
- Fast Track designation from the FDA
- Rare Paediatric Disease designation from the FDA
Both Neuren drug candidates target the critical role of Insulin-like growth factor 1 (IGF-1) in the brain, using orally administered analogues of naturally occurring peptides. This platform approach positions Neuren to address multiple serious neurological disorders caused by genetic abnormalities or brain injury that have no or limited approved treatment options.
The pipeline diversification means Neuren is not solely dependent on European trofinetide approval, while any positive outcome from the Neuren trofinetide CHMP re-examination would provide additional royalty upside from a significant new market.
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What investors should watch next
Several key milestones will determine the outcome of the Neuren trofinetide CHMP re-examination over the coming months:
- Acadia’s formal submission of the re-examination request to the EMA (must occur within 15 days of receiving the negative opinion)
- EMA acceptance of the request and assignment of a new rapporteur panel to conduct the review
- Re-examination outcome, expected approximately 60 days from formal acceptance of the request
Throughout this process, Neuren will continue to receive royalties from trofinetide sales in the United States, Canada, and Israel, where the therapy remains the only approved treatment for Rett syndrome. These existing revenue streams provide financial stability independent of the European regulatory outcome.
The re-examination represents a defined catalyst with a clear timeline, allowing shareholders to monitor progress over a 2-3 month period from formal submission. A positive outcome would open access to the European market, where the unmet medical need remains substantial according to management commentary and patient advocacy groups.
For ASX: NEU shareholders, the parallel advancement of the Koala Phase 3 trial for NNZ-2591 in Phelan-McDermid syndrome provides a second near-term value driver, reducing concentration risk around the European trofinetide decision.
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