Neuren Pharmaceuticals (ASX:NEU) has received formal feedback from the US Food and Drug Administration (FDA) on the next stages of clinical development for its lead pipeline asset, NNZ-2591, across hypoxic ischemic encephalopathy (HIE) and Pitt Hopkins syndrome (PTHS), providing greater regulatory clarity for its rare disease programs at a time of heightened scrutiny on global regulatory execution.
The feedback followed a Type B pre-Investigational New Drug (IND) meeting request for HIE and a Type C meeting for PTHS. In both cases, the FDA elected to respond via Written Responses Only, a process Neuren noted was delayed relative to agency goal timelines but nonetheless delivered actionable guidance. CEO Jon Pilcher said the company now has a clear path forward for both programs, with minimal financial impact and sufficient funding to advance development.
For HIE, the FDA generally accepted Neuren’s proposed IND-opening clinical study, which will evaluate the pharmacokinetics, tolerability and safety of NNZ-2591 over one month in neonates and infants. While the agency provided guidance on dosing, inclusion and exclusion criteria, and safety monitoring, it also requested additional data from juvenile animals to support neonatal dosing. Neuren plans to generate this data ahead of submitting its IND and commencing the clinical study later in 2026, while continuing to advance the logistical requirements for execution. The FDA also encouraged further engagement to align on endpoints and study design for a subsequent registration-supporting trial.
In Pitt Hopkins syndrome, FDA feedback indicated that efficacy could be demonstrated using a PTHS-specific clinical global impression scale as a co-primary endpoint, provided it is paired with an observer-reported functional outcome measure. This mirrors the endpoint framework already in use in Neuren’s ongoing Phase 3 trial of NNZ-2591 for Phelan-McDermid syndrome, its lead indication. Given the ultra-rare nature and greater clinical severity of PTHS, Neuren is assessing alternative trial designs and analytical approaches and expects to re-engage with the FDA before finalising the program. Initiation of the next PTHS trial remains targeted for 2026.
The progress in the United States contrasts with a more challenging near-term regulatory outlook in Europe for Neuren’s approved Rett syndrome therapy, trofinetide, which is licensed to Acadia Pharmaceuticals. Acadia recently disclosed that it had received a negative trend vote from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency regarding its marketing authorisation application for trofinetide in the European Union. While the outcome was described as disappointing, Acadia has indicated it intends to seek re-examination of the CHMP opinion, citing extensive clinical trial data and real-world use across more than 1,000 patients globally.
Neuren has publicly supported Acadia’s intention to pursue re-examination, noting the frustration for the European Rett syndrome community given trofinetide’s approvals in the United States, Canada and Israel. The European process, which allows for formal re-examination within defined statutory timeframes, introduces a degree of regulatory uncertainty that sits alongside Neuren’s otherwise advancing US-focused development strategy.