Does NNZ-2591 work?
Not properly: animal or lab studies, or small uncontrolled human reports. One report of 18 children.
The only published trial is a single-group, open-label phase 2 study in 18 children with Phelan-McDermid syndrome, designed mainly to test safety and drug levels. Without a placebo group, the reported improvements on caregiver and clinician scales cannot be separated from expectation effects. A placebo-controlled phase 3 trial in children started in November 2025. It is recruiting. 124
The published phase 2 trial enrolled children aged 3 to 12 with Phelan-McDermid syndrome. Loss of the SHANK3 gene causes this condition. Eighteen children took oral NNZ-2591 twice a day for 13 weeks. All of them got the drug, and there was no placebo arm. The main outcomes were safety and pharmacokinetics, which means how the body absorbed and cleared the drug. Caregivers and clinicians also filled in 14 secondary measures of whether it works. 12
Most adverse events were mild to moderate. No serious safety concerns emerged. On the 14 measures, 10 showed significant improvement from baseline. On the clinician-rated global impression scale, 16 of 18 children improved. The trial was open-label. Caregivers and clinicians knew every child was getting the drug. So part of this could reflect expectation. The company reports that a similar open-label trial in Pitt Hopkins syndrome also met its goals. A randomized, placebo-controlled phase 3 trial in children with Phelan-McDermid syndrome started in November 2025. It is recruiting. 134
Evidence checklist
- Randomised controlled trial Open-label, single-group phase 2
- Human study over 100 people 18 children
- More than one research group Article does not say
- Clinical outcomes, not surrogate markers Caregiver and clinician rating scales
- Human safety data beyond case reports 13-week trial; no safety withdrawals; short
More on NNZ-2591
Citations
- Neumeyer 2025 (published online December 2025; Feb 2026 issue), Neurology Genetics: NNZ-2591 in children and adolescents with Phelan-McDermid syndrome, single-group open-label phase 2 trial doi.org
- ClinicalTrials.gov NCT05025241: an open-label study of oral NNZ-2591 in Phelan-McDermid syndrome (PMS-001) clinicaltrials.gov
- BioWorld 2024: Neuren's NNZ-2591 meets phase 2 endpoints in Pitt Hopkins syndrome (company report) bioworld.com
- ClinicalTrials.gov: NCT07281079, phase 3 trial of NNZ-2591 in Phelan-McDermid syndrome clinicaltrials.gov
Reference information only, not medical advice. Drawn from the NNZ-2591 article, fact-checked against the cited sources. No dosing anywhere on this site.