Neuren Pharmaceuticals Limited announced that its Phase 2 clinical trial of NNZ-2591 in Angelman syndrome (AS) is open for enrolment. The first subjects are expected to enter the trial imminently at the Centre for Clinical Trials in Rare Neurodevelopmental Disorders at Children's Health Queensland Hospital. The trial is being conducted at three hospitals in Brisbane, Melbourne and Sydney under an Investigational New Drug application (IND) with US Food and Drug Administration.

Top-line results are anticipated for H1 2023. The open label Phase 2 trial (NCT05011851) will enrol a single group of up to 20 children aged 3 to 17 years with AS to examine safety, tolerability, pharmacokinetics and efficacy over 13 weeks of treatment with NNZ-2591. All subjects will receive NNZ-2591 as an oral liquid dose twice daily, with titration up to the target mg/kg dose during the first 6 weeks of treatment, subject to safety and tolerability.

The treatment period is preceded by 4 weeks of observation to thoroughly examine the baseline characteristics prior to treatment, against which safety and efficacy will be assessed for each child. A follow-up assessment will be made 2 weeks after end of treatment. The primary outcome measures are safety and tolerability, including the incidence, severity and frequency of adverse events, as well as measures of standard pharmacokinetic parameters.

Secondary outcome measures include a range of exploratory efficacy measures completed by clinicians and caregivers. The overall aim of the Phase 2 trial is to generate information to inform the design of a subsequent registration trial. In parallel with the Phase 2 trial, Neuren is also executing the foundational work to prepare for Phase 3 development across multiple indications.

There are currently no approved medicines for AS, which is characterized by severe developmental delay and learning disabilities that become noticeable by the age of 6 - 12 months. Children and adults with AS typically have balance issues, motor impairment and can have debilitating seizures. Some individuals never walk, most do not speak and disruptive sleep also can be a serious challenge.

Individuals have a normal life expectancy, but they require continuous care and are unable to live independently. AS is caused by a loss of function of the UBE3A gene on chromosome 15, with incidence estimated at between 1 in 12,000 and 1 in 24,000 people.