Neuren Advances NNZ-2591 with FDA Guidance for HIE and Pitt Hopkins Syndrome

FDA Feedback Shapes Next Steps

Neuren Pharmaceuticals (ASX, NEU) has taken a significant step forward in the clinical development of its drug candidate NNZ-2591, following recent interactions with the US Food and Drug Administration (FDA). The company received written responses from the regulator regarding its plans to treat two rare and serious neurological disorders, hypoxic ischemic encephalopathy (HIE) and Pitt Hopkins syndrome (PTHS). While the feedback came later than expected and was limited to written form, it nonetheless provides a clearer roadmap for Neuren’s upcoming clinical activities.

Hypoxic Ischemic Encephalopathy, Preparing for Clinical Trials

HIE is a devastating brain injury occurring in newborns due to insufficient oxygen or blood flow around birth, often resulting in lifelong disabilities. Neuren’s proposed initial clinical study aims to evaluate the safety, tolerability, and pharmacokinetics of NNZ-2591 in neonates and infants over a month-long period. The FDA has generally accepted this approach and the dosing regimen, but has requested additional juvenile animal study data to better support dosing decisions before the trial can commence. Neuren plans to generate this data and submit its Investigational New Drug (IND) application later in 2026, signalling a cautious but steady progression toward clinical evaluation.

Pitt Hopkins Syndrome, Navigating Trial Design Challenges

Pitt Hopkins syndrome, a rare neurodevelopmental disorder characterised by intellectual disability and other severe symptoms, presents unique challenges for clinical trial design due to its rarity and severity. The FDA’s feedback suggests that a controlled trial could use a PTHS-specific clinical global impression scale as a co-primary endpoint, paired with an observer-reported functional outcome measure. This mirrors the approach Neuren is already implementing in its Phase 3 trial for Phelan-McDermid syndrome, another rare disorder. However, Neuren is still exploring alternative trial designs and endpoint analyses to accommodate PTHS’s distinct characteristics, with further FDA discussions anticipated before trial initiation later this year.

Financial Position and Forward Outlook

Despite the delays and the need for additional data, Neuren’s CEO Jon Pilcher emphasised that the company remains well positioned financially to advance both programs with minimal impact. The commitment to addressing urgent unmet needs in these rare disorders remains strong, and investors can expect an update soon on the ongoing Koala Phase 3 trial in Phelan-McDermid syndrome, which is the lead program for NNZ-2591. This trial’s progress will be closely watched as a bellwether for the drug’s broader clinical potential.

Rare Diseases and Orphan Drug Incentives

Both HIE and PTHS have been granted orphan drug designation in the US and EU, recognising the critical need for effective therapies in these underserved patient populations. This status provides regulatory incentives that can accelerate development and commercialisation, underscoring the strategic importance of NNZ-2591 within Neuren’s pipeline. The company’s approach reflects a growing trend in biotechnology to focus on rare neurological conditions where treatment options are limited or non-existent.