Is NNZ-2591 FDA-approved, and what does the research show?

What is NNZ-2591?

NNZ-2591 is an investigational drug, studied in children and adolescents with rare genetic conditions that affect how the brain develops ¹, ², ³. It is not a wellness, weight-loss or performance product: every patient trial cited here that enrolled anyone is in children or adolescents with a diagnosed genetic syndrome ¹, ⁵, ², ³, ⁶.

NNZ-2591 is the name its trials use, and the trial registry also lists a chemical name, cyclo-L-glycyl-L-2-allylproline ². The published trial describes it as "a synthetic analog of the insulin-like growth factor 1 metabolite cyclic glycine-proline" ¹. Insulin-like growth factor 1, or IGF-1, is a natural growth factor that "plays an important role in brain development, maturation, and neuroplasticity," the brain's ability to adapt its wiring ¹. A metabolite is a substance the body makes as it breaks another down, and an analog is a modified copy. Cyclic glycine-proline, as its name says, is two amino acids, glycine and proline, joined in a ring.

Phelan-McDermid syndrome is a rare genetic condition caused by a missing piece of chromosome 22 or a harmful change in a gene called SHANK3 ¹. People with it can have developmental delay, intellectual disability and "absent or severely impaired speech" ¹.

Pitt Hopkins syndrome is another rare genetic condition that brings developmental delay and intellectual disability. Angelman syndrome is a third, marked by developmental delay and severe difficulty with speech. The entry rule of the Angelman trial carries the words "known to impact maternally derived UBE3A expression in brain" ³. UBE3A is a gene, and "maternally derived" means the copy inherited from the mother.

Neuren Pharmaceuticals, an Australian company, sponsors the trials and funded the published one ¹, ⁵. In the two trials whose results are cited here, the drug was a liquid swallowed twice a day ¹, ², ⁷.

Is NNZ-2591 FDA-approved?

NNZ-2591 is not FDA-approved: Drugs@FDA lists no approved NNZ-2591 product as of November 9, 2026 ⁴. It is an investigational drug whose phase 3 trial in children with Phelan-McDermid syndrome reads "Recruiting" in its registry record, last update posted September 28, 2026 ⁵. Drugs@FDA lists no approved NNZ-2591 product, so no FDA label, the document that carries FDA-reviewed prescribing and safety information, is cited here ⁴.

The registry describes that trial as "randomized, double-blind, parallel-group (2-arm), placebo-controlled" ⁵. In plain words, children are assigned by chance to the drug or a dummy liquid, a placebo, and neither families nor investigators know which. Its estimated enrollment is 160 children aged 3 to 12 ⁵. The record estimates primary completion, the last visit for the main measures, for October 2027 ⁵. A second phase 3 study, for children continuing from the earlier studies, also reads "Recruiting," last update posted November 9, 2026, with an estimated enrollment of 180 ⁶.

No source cited here shows a way to obtain NNZ-2591 outside a clinical trial. None of the seven registry records cited here offers expanded access, the supply of an unapproved drug to a patient outside a trial ⁵, ², ³, ⁶, ⁷, ⁸, ⁹.

Compounding is the mixing or preparing of a medicine outside a drug maker's FDA-approved production. FDA keeps two lists of bulk drug substances, the raw active ingredients, nominated for compounding: one under section 503A of the federal drug law, one under section 503B. Section 503A covers pharmacies filling a prescription for a named patient, and section 503B covers outsourcing facilities, which may compound without one.

The 503A list, updated May 14, 2026, does not name NNZ-2591 or cyclic glycine-proline ¹⁰. Nor does the 503B list, updated March 21, 2025 ¹¹. Neuren, the sponsor, says it is "unable to offer a compassionate use program" at this time and points patients to its trials ¹².

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How does NNZ-2591 work?

The published trial gives a hypothesis of how NNZ-2591 works, not a demonstrated mechanism ¹. The starting point is the natural molecule it copies. "Cyclic glycine-proline regulates IGF-1 bioavailability and homeostasis through an autoregulatory mechanism," the paper says ¹. In plain words, it helps set how much IGF-1 is free to act and keeps that amount steady. NNZ-2591 is "hypothesized to treat PMS," that is, Phelan-McDermid syndrome, "by mimicking the natural actions of cyclic glycine-proline in maintaining IGF-1 homeostasis" ¹.

The interest in IGF-1 comes from laboratory work on the natural growth factor, not on NNZ-2591. Studied in animals and shown in cells: the paper says "treatment with IGF-1 led to improvements" in Shank3-deficient mice and in nerve cells grown from patients' stem cells ¹.

Proposed: the authors name three ways the drug acts, by its mechanism of action. They are "restoring depressed bioavailability of IGF-1, reducing overactivity of the mitogen-activated protein kinase/extracellular signal–regulated kinase (MAPK/ERK) signaling pathway (which is crucial for synaptic plasticity), and decreasing expression of inflammatory signaling molecules" ¹. The MAPK/ERK pathway is a chain of signals inside cells, and inflammatory signaling molecules are the chemical messengers of inflammation. Synaptic plasticity is the capacity of the connections between nerve cells to strengthen or weaken. The paper names these as the drug's mechanism of action, and the trial itself measured safety, drug levels and symptom ratings ¹.

The trial also modeled how long the drug stays in the body. Its estimated half-life, the time for half of it to leave the blood, was 7.4 hours in a typical child weighing 30 kilograms ¹.

What does the research show?

Studied in people: a single-group, open-label phase 2 trial, 18 participants with Phelan-McDermid syndrome, with safety and drug levels as its primary end points ¹, ⁷. Open-label means everyone knew the participant was taking the drug, and single-group means there was no placebo or other comparison group. Phase 2 is the middle stage of testing, and an end point is a measure a trial sets in advance. With everyone aware of the treatment and no comparison group, a change measured in the trial cannot be told apart from what time or hope alone would bring.

The paper appeared online on December 23, 2025, in the journal's February 2026 issue ¹. The journal published a correction to it on June 17, 2026 ¹³. The text of the correction is not among the sources cited here. Every figure from the paper given here, in any section, is from Europe PMC's copy of its full text, and the correction may affect some of them ¹, ¹³. against the corrected paper]

Entry required, among other criteria, an age of 3 to 12 at screening, a clinical diagnosis and a disease-causing genetic change affecting SHANK3 ¹. The participants took NNZ-2591 for 13 weeks, with two weeks of follow-up, at four sites in the United States ¹. Eighteen enrolled and received the drug, and 15 completed the study ¹. The planned sample was 20 ¹.

Efficacy was a secondary end point, tracked on 14 assessments, and each result is a change against the child's own starting point ¹. The paper reports statistically significant improvement on 10 of the 14 at week 13 ¹. Statistically significant means the change was unlikely to be chance alone under the test used. The four that did not reach it were a second quality-of-life scale, two communication measures and a composite score of adaptive behavior ¹.

The trial was sized on a clinician's rating, the Clinical Global Impression of Improvement, in a version written for this syndrome ¹. It runs from 1 to 7: 4 means no change, and lower scores mean improvement ¹.

At the end of treatment (week 13, or earlier for the three who left), among all 18, the mean score was 2.4 and the median 2.0 ¹, ⁷. Clinicians rated 16 of the 18 participants as improved ¹. On the matching caregiver scale, the Caregiver Impression of Change, the mean was 2.7, and caregivers rated 15 of 18 as improved ¹. On the clinician's severity scale, 7 of 18 improved by one point ¹.

The authors state the limits themselves. The study "was open label and did not include a placebo comparator," and clinician and caregiver ratings "may be subject to expectancy bias" ¹. Expectancy bias is the pull of hope on a rating when the rater knows the child is being treated. No adjustment was made for testing many measures, "which increased the risk of type I error," a false positive ¹. The authors call the results "preliminary evidence of efficacy" ¹.

The paper says five of the scales were developed for this trial, and that no widely accepted rating scale for the syndrome exists for use in clinical trials ¹. Neuren funded the study and took part in its design, analysis and writing, and three of the eight authors are Neuren executives ¹.

Studied in people: a single-group, open-label phase 2 trial in Pitt Hopkins syndrome, ages 3 to 17, with 13 weeks of treatment ². Its results are the sponsor's postings on the registry; no journal paper on this trial is cited here. The record counts 28 enrolled: 12 did not pass screening, 16 began treatment and 11 completed it ².

Among the 11 analyzed, the clinician's improvement rating averaged 2.6 on a 1-to-7 scale where lower is better ². Of the 15 secondary measures posted, four carry a p-value below 0.05, the usual line for statistical significance ². They are the clinician's and the caregiver's overall ratings, the clinician's severity rating and the caregivers' top three concerns ². The other 11, among them scales of behavior, sleep, communication and quality of life, do not ². The trial had one group, so each p-value tests a change within the same children, not a difference from a comparison group ².

Studied in people: a third open-label phase 2 trial of the same length, in Angelman syndrome, at three sites in Australia ³. The registry records it as completed, with 17 enrolled under an entry age of 3 to 17 ³. None of the sources cited here reports results from that trial, and its record, last update posted January 31, 2025, showed none when read on November 10, 2026 ³.

Studied in people: a phase 1 trial in healthy adults, also in Australia, completed in February 2021, with an enrollment of 28 on its registry record ⁸. Phase 1 is the first stage of testing in people, mainly for safety. It tested single and repeated doses for safety and drug levels, the repeated doses against placebo ⁸. A further trial, planned in Prader-Willi syndrome, a rare genetic condition that affects growth, appetite and development, was withdrawn before anyone enrolled ⁹. The registry gives the reason as "Revised development strategy" ⁹.

Of the trials cited here, one tests NNZ-2591 against placebo in patients: the phase 3 trial in Phelan-McDermid syndrome ⁵. Assignment is one to one, and treatment lasts 13 weeks ⁵. One primary measure at week 13 is the Phelan-McDermid Syndrome Assessment of Change, scored from 1, very much improved, to 7, very much worse ⁵. The other is a score for receptive communication, the understanding of language, from the Vineland Adaptive Behavior Scales ⁵.

The second phase 3 study, an extension, gives every child NNZ-2591 open-label for 52 weeks ⁶. None of the sources cited here reports results from a placebo-controlled trial in patients, from treatment beyond 13 weeks, or from adults with these syndromes ¹, ⁵, ², ³, ⁶. The two phase 3 studies address the first two, for children with Phelan-McDermid syndrome only ⁵, ⁶.

What are the side effects?

The safety record cited here is small and has no comparison group ¹, ². The authors say blinded, placebo-controlled studies "will enhance understanding of the safety and efficacy of NNZ-2591" ¹. In the Phelan-McDermid trial, 17 of 18 participants had at least one adverse event, and "Most TEAEs were mild to moderate in severity" ¹. TEAE stands for treatment-emergent adverse event: any health problem that starts or worsens after the first dose, whatever its cause.

The most common event was psychomotor hyperactivity, in four children ¹. COVID-19, decreased appetite, fever and sleepiness were each reported in three ¹. In trial reporting, "severe" grades how intense an event is, while "serious" is a separate term for an event that leads, for example, to a hospital stay. One event was rated severe: hyperactivity, "considered possibly related to the study drug," which resolved the next day with no change of dose ¹. One serious event, a mild gastroenteritis during follow-up, was considered unrelated ¹.

Three participants left the study because of adverse events, two with COVID-19 and one with seizures, none considered related to the drug ¹. No deaths were reported ¹. The paper reports no clinically significant changes in laboratory values or electrocardiograms, the tracings of the heart's rhythm ¹.

In the Pitt Hopkins trial, 15 of the 16 children treated had an adverse event, by the sponsor's registry posting ². None was serious or severe, and no child died ². Four children stopped because of an adverse event ². Diarrhea and fatigue were the most frequent, in four children each, then constipation and nasopharyngitis, a cold, in three each ².

The phase 3 trial's entry rules leave out children with abnormal liver test results, an abnormal QT interval on an electrocardiogram, or recent seizures ⁵. The QT interval is the time the heart's lower chambers take to fire and reset with each beat.

In sport

NNZ-2591 is not named on the 2026 Prohibited List of WADA, the World Anti-Doping Agency, and neither is cyclic glycine-proline ¹⁴. Section S2.3 of the list, on growth factors, names "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues" ¹⁴. The published trial describes NNZ-2591 as "a synthetic analog of the insulin-like growth factor 1 metabolite cyclic glycine-proline" ¹.

Section S0 of the list prohibits at all times "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development or discontinued, designer drugs, substances approved only for veterinary use)" ¹⁴. FDA is the only regulator whose records are cited here, and it lists no approved NNZ-2591 product ⁴. Which section, if any, covers NNZ-2591 is for anti-doping authorities to say.

What JumpstartMD offers

JumpstartMD does not prescribe NNZ-2591. Our peptide library covers it so you have the facts on its FDA status and the evidence, current as of November 10, 2026.

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Compounded medications are not FDA-approved, and FDA does not review their safety, effectiveness, or quality before they are marketed. A licensed clinician decides after an evaluation whether a peptide is appropriate for you, and not every patient will qualify.