Neuren Pharmaceuticals announced the submission of an Investigational New Drug (IND) application for NNZ-2591 in Prader-Willi syndrome and provided an update on progress in its ongoing Phase 2 clinical trials for each of Phelan-McDermid, Angelman and Pitt Hopkins syndromes. Neuren's drug NNZ-2591 is being developed for these four serious neurological disorders that emerge in early childhood and for which there are no approved medicines. The new IND application was submitted to the US Food and Drug Administration (FDA) on 22 December for approval to proceed with a Phase 2 trial in Prader-Willi syndrome.

Clinical trials are currently ongoing in each of the other three syndromes, which are the first trials of NNZ-2591 in children with each syndrome. The open label Phase 2 trials are each enrolling up to 20 children to examine safety, tolerability, pharmacokinetics and efficacy over 13 weeks of treatment with NNZ-2591. All subjects receive NNZ-2591 as an oral liquid dose twice daily, with escalation in two stages up to the target dose during the first 6 weeks of treatment, subject to independent review of safety and tolerability data.

The trials are enrolling subjects in three age groups. Safety and tolerability data in the oldest age group must be independently reviewed before proceeding with dosing in the second age group and then safety and tolerability data in the second age group must be independently reviewed before proceeding with dosing in the youngest age group. The study begins with 4 weeks of observation to thoroughly examine baseline characteristics prior to treatment, against which safety and efficacy are assessed for each child.

This is followed by the treatment period of 13 weeks. A follow-up assessment is made 2 weeks after the end of treatment. In the Phelan-McDermid syndrome trial and in the Angelman syndrome trial, the first subject in the oldest age group has now completed the treatment period of 13 weeks, with a good safety and tolerability profile.

Each subject was successfully escalated up to the target dose following safety and tolerability reviews by an independent data and safety monitoring committee (DSMC). No serious adverse events were reported and no dose modifications were required. Most of the adverse events reported were mild and not considered to be related to study drug.

There were no clinically relevant observations in safety laboratory measurements or cardiac tests. In the Phelan-McDermid trial, enrolment in the second age group was approved following review by the DSMC of safety and tolerability data for subjects in the oldest age group. The number of potential subjects identified for each trial exceeds the total requirement, however the restriction of enrolling subjects in three age groups sequentially commencing with the oldest is a constraint, delaying the start of the trial for younger subjects.

Neuren is working closely with the patient communities and trial sites to accelerate enrolment after the holiday period in the first half of 2023 as younger age groups are activated. The four trials will likely complete at different times, with a series of top-line results announcements now anticipated from H2 2023, commencing with Phelan-McDermid syndrome.