Phase 2 Trial of NNZ-2591 for Angelman Opens in Australia

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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A Phase 2 trial of NNZ-2591, Neuren Pharmaceuticals’ investigational oral therapy for Angelman syndrome, has started recruiting pediatric patients in Australia.

The Australian study — which was also given regulatory clearance in the U.S. — will be conducted at three hospitals in that country: one each in Queensland, New South Wales, and Victoria.

Eligible children are now being enrolled at the Centre for Clinical Trials in Rare Neurodevelopmental Disorders at Children’s Health Queensland Hospital in South Brisbane, Queensland. Detailed site information and general contact information are available.

Top-line results are expected in May 2023.

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“We are excited to commence this trial in Australia to assess the potential for NNZ-2591 to make a difference in Angelman syndrome, a seriously debilitating condition with no approved medicines,” Jon Pilcher, CEO of Neuren, said in a press release.

NNZ-2591 is a compound with a chemical structure similar to the cyclic glycine proline — a small protein important for the development of nerve cells. The investigational treatment is meant to restore the normal communication and signaling between brain cells.

In preclinical studies with mice genetically engineered to lack the UBE3A gene (called knockout mice) treatment with NNZ-2591 improved cognition and motor function, reduced anxiety, and prevented seizures.

“In the ube3a knockout mouse model of Angelman, treatment with NNZ-2591 normalized all the deficits, so we are now eager to observe the effects of treatment in children,” Pilcher said.

The open-label and dose-escalating study (NCT05011851) plans to enroll up to 20 children, ages 3 to 17, with a confirmed diagnosis of Angelman syndrome.

Following an initial four-week observation and assessment period, all will be given NNZ-2591 as an oral solution twice daily for 13 weeks (about three months).

NNZ-2591 dosing will gradually increase during the trial’s first six weeks, subject to safety and tolerability, until a target dose of 50 milligrams per milliliters (mg/mL) is reached. A follow-up assessment will be conducted two weeks after finishing treatment.

The trial’s main goal is to assess NNZ-2591’s safety and tolerability, and its pharmacokinetics, which refers to the movement of a compound into, through, and out of the body.

Additional or secondary goals are exploratory measures of treatment efficacy, completed by clinicians and caregivers. These include whether the patient has improved or worsened with treatment using various Angelman syndrome-specific Clinical Global Impression scales, and caregivers’ impressions of change.

Findings in the Phase 2 trial are expected to aid in the design of a larger and registrational trial, a mandatory step for any future application seeking NNZ-2591’s approval to treat Angelman syndrome.