NNZ-2591: evidence, FDA status and research

It is a pill being tested for rare genetic conditions linked to autism. The one published trial had 18 children and no comparison group, and a placebo-controlled trial began in 2025.

Sold for

NNZ-2591 is talked about as a follow-on to trofinetide, a possible oral treatment for several genetic autism-related syndromes at once.

Studies say

One small uncontrolled trial found the drug was tolerated and that scores moved in a favorable direction, which is the kind of evidence that justifies a placebo-controlled trial but does not show the drug works.

Why grade C. 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

FDA. Not approved by the FDA for any use. NNZ-2591 is an investigational oral drug from Neuren Pharmaceuticals being tested in rare neurodevelopmental disorders, and the published human data are from an open-label phase 2 trial in Phelan-McDermid syndrome. A randomized, placebo-controlled phase 3 trial in children with Phelan-McDermid syndrome started in November 2025 and is recruiting.

Written from 4 cited sources. Fact-checked 2026-10-27: 12 claims checked, 1 corrected, 1 sources unreachable. Independent check by a second model (2026-10-28): 2 points flagged. Last refreshed 2026-10-27. Not physician reviewed.

What this means for you

What people take it for: Rare genetic brain development conditions
Can a US doctor prescribe it?: Not yet; it is still in trials.
Properly tested in people?: Not properly: animal or lab studies, or small uncontrolled human reports. One report of 18 children.

Evidence checklist

Randomised controlled trial Open-label, single-group phase 2no
Human study over 100 people 18 childrenno
More than one research group Article does not sayno information
Clinical outcomes, not surrogate markers Caregiver and clinician rating scalesno
Human safety data beyond case reports 13-week trial; no safety withdrawals; shortyes

Drawn from the cited studies below. A dash means the sources give no information.

What it is

NNZ-2591 is a small lab-made molecule. It is modeled on cyclic glycine-proline, a natural breakdown product of insulin-like growth factor 1 (IGF-1). Neuren Pharmaceuticals developed it. This Australian company is also behind trofinetide. NNZ-2591 is an oral liquid. It is more stable in the body than the natural compound. ¹

The company is testing it in Phelan-McDermid syndrome, Pitt Hopkins syndrome, Angelman syndrome and Prader-Willi syndrome. All four are rare genetic conditions. They cause intellectual disability and autism-like features. The Phelan-McDermid trial is the one with published results. ¹²

How it works

IGF-1 signaling helps control how neurons grow, connect and prune their connections. In several genetic neurodevelopmental disorders, this signaling seems out of balance. Cyclic glycine-proline is thought to bring IGF-1 activity back to normal. It changes how much of the hormone is free to act on its receptor. It does not simply add more hormone. NNZ-2591 is designed to do the same thing. It survives digestion and lasts longer in the bloodstream. ¹

What human research shows

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

Study	Model	Finding
PMS-001 phase 2 (Neumeyer 2025)	Humans, n=18 children with Phelan-McDermid syndrome, single-group open-label	NNZ-2591 was tolerated over 13 weeks, with improvement reported on 10 of 14 secondary efficacy scales in the absence of a control group. ¹
NCT05025241 registration	Humans, children aged 3 to 12, open-label	Trial registry entry describing the design, primary safety and pharmacokinetic endpoints. ²

Safety

In the 13-week trial, adverse events that appeared during treatment were mostly mild or moderate. No one died or stopped treatment for safety reasons. That is reassuring but limited. A study of 18 children over three months cannot reveal uncommon side effects. It cannot show anything about long-term use. There are no data in adults. There are none on effects outside the trial groups. ¹

Questions for your clinician

Is a placebo-controlled trial running?
How can improvement be told apart from expectation in an open-label study?
What is known about use beyond three months?

Questions people ask

How is NNZ-2591 related to trofinetide?

Both come from Neuren. Both are lab-made versions of natural IGF-1 fragments. Trofinetide is based on the N-terminal tripeptide of IGF-1. It is approved for Rett syndrome. NNZ-2591 is based on cyclic glycine-proline, a different IGF-1-related molecule. It is still in trials. ¹

Did the trial show NNZ-2591 works?

It showed the drug was tolerated. Scores improved on most scales. But every child got the drug and families knew it. So the gain cannot be told apart from the hope and attention that come with being in a trial. Only a placebo-controlled study can show whether it works. A phase 3 trial of that kind started in November 2025 and is recruiting. ¹⁴

Is NNZ-2591 sold online as a research peptide?

It appears on some research-chemical sites. But it is a small molecule, not a classic peptide. Researchers have tested it only in children with specific genetic syndromes. There are no data on its effects in anyone else. ¹

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

Independent check

A second model (claude-opus-5-5) read this article against the abstracts of its cited papers on 2026-10-28 and flagged these points. It saw abstracts only, so a flag can mean the detail sits in the full paper or a source without text. Flags are published as found until an editor resolves them.

mediumThe published phase 2 trial enrolled children aged 3 to 12 with Phelan-McDermid syndrome. The title of source [1] describes the trial population as 'children and adolescents with Phelan-McDermid syndrome', which suggests an age range beyond 12; the 3 to 12 range is not supported by any provided text [1]
lowA randomized, placebo-controlled phase 3 trial in children with Phelan-McDermid syndrome started in November 2025 and is recruiting. not in the cited sources; this sentence has no citation in the fda section, and the matching source [4] has no text provided

Updates

2026-10-27 Fact-checked against the cited sources: 12 claims checked, 1 corrected.
2026-10-27 FDA status re-checked against FDA sources: added phase 3: randomized placebo-controlled trial in pediatric Phelan-McDermid syndrome (NCT07281079) started 2025-11-12, recruiting.