Peptide education
NNZ-2591
Ercanetide
NNZ-2591, also called ercanetide, is an investigational synthetic analog of cyclic glycine-proline, a molecule related to insulin-like growth factor 1. It is being studied in rare neurodevelopmental disorders.
In an open-label study of 18 children with Phelan-McDermid syndrome, some clinical ratings improved from baseline. Without placebo, those changes cannot establish a drug effect. A controlled phase 3 trial is recruiting.
Overview
Quick answer
NNZ-2591 and trofinetide, also called NNZ-2566, are different compounds. Trofinetide's U.S. Rett syndrome approval does not apply to NNZ-2591.
Is NNZ-2591 approved?
The compound remains investigational. An openFDA exact active-ingredient search for ercanetide returned no match; other names and jurisdictions require separate checks.
What did the open-label study show?
Eighteen children received NNZ-2591. Investigators reported improvement from baseline on 10 of 14 secondary efficacy assessments. A placebo group is needed to interpret whether treatment caused those changes.
What is the next controlled test?
A registered phase 3 trial compares NNZ-2591 with placebo in children with Phelan-McDermid syndrome for 13 weeks. The registry lists it as recruiting and has no posted results.
Is this the same medicine as DAYBUE?
No. DAYBUE contains trofinetide, also called NNZ-2566. NNZ-2591 is a different investigational molecule with a separate clinical program.
Evidence
Evidence snapshot
Safety and pharmacokinetics were primary outcomes; efficacy assessments were secondary.
Changes from baseline cannot establish that the drug caused improvement.
The registry describes the design, not a completed efficacy result.
The clinical protocol reports behavioral findings in Shank3b knockout mice.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| NNZ-2591 is proven to treat Phelan-McDermid syndrome. | The published phase 2 study reported changes from baseline, but all participants received the drug and families and clinicians knew it. | A sponsor protocol also summarizes findings in a genetic mouse model. Those results are not clinical proof. | Clinical benefit remains unconfirmed pending controlled results. |
| A registered phase 3 trial means efficacy has been confirmed. | The registry describes a randomized, blinded comparison with placebo and lists it as recruiting, with no posted results. | A trial registration is not a trial result. | |
| NNZ-2591 and trofinetide are interchangeable. | The sponsor lists NNZ-2591 and trofinetide as separate compounds and development programs. | Their study findings and regulatory status should not be combined. |
Bottom line
Main takeaway
An early uncontrolled study reported changes in clinical ratings, but it did not establish that the drug caused them.
Placebo-controlled benefit, uncommon adverse events, and longer-term safety remain uncertain.
Read the corrected phase 2 safety table alongside the publication and distinguish the sponsor's mouse summary from a full animal paper.
Identity
What it is
NNZ-2591 is a synthetic analog of cyclic glycine-proline, described in the phase 2 paper as an IGF-1 metabolite.
It is a different compound from trofinetide, although both programs are connected to IGF-1-derived research.
Use context
Routes, doses, and cycle patterns
The Phelan-McDermid study used a weight-based oral regimen; the animal experiment used a separate exposure.
Human studies and product labels
Phelan-McDermid phase 2 study
- Purpose
- Safety, pharmacokinetics, and exploratory clinical assessments
- Context
- Study-reported human regimen
- Route
- Oral liquid
- Amount
- 4 mg per kg, then 8 mg per kg, then 12 mg per kg per dose
- Frequency
- Twice daily
- Duration
- 13 weeks, with approximately three weeks at each initial dose
The target dose was reached after approximately six weeks, subject to study safety review.
Shank3b knockout mouse experiment
- Purpose
- Behavioral and seizure measurements
- Context
- Sponsor protocol summary, animal study only
- Route
- Oral
- Amount
- 100 mg per kg per day
- Frequency
- Daily total; number of administrations not stated
- Duration
- Six weeks
The protocol also mentions 200 mg per kg without a time denominator. A separate pharmacokinetic comparison describes a different mouse exposure.
What varies
- The phase 2 study used a weight-based escalation with safety review. That schedule is specific to the study population and formulation.
- The phase 3 registry describes twice-daily oral administration, but it is not a source of confirmed outcomes.
Research
Research evidence
A small uncontrolled Phelan-McDermid study reported changes from baseline. A sponsor protocol summarizes an earlier healthy-volunteer safety study, and a separate randomized study is intended to compare treatment with placebo.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Phelan-McDermid phase 2 | 18 participants aged 3 to 12 years at screening, 15 completed | Single-group, open-label study | Oral NNZ-2591 twice daily for 13 weeks, with the target dose reached after approximately six weeks | Changes from baseline were reported on 10 of 14 secondary efficacy assessments | No placebo group, small sample, multiple exploratory assessments | Preliminary uncontrolled human evidence |
| Healthy-volunteer phase 1 study | 28 healthy adult volunteers | Open-label single-dose cohorts and randomized, blinded multiple-dose cohorts, summarized in the sponsor protocol | Oral NNZ-2591 in a short safety and pharmacokinetic study | The protocol reports drug-related drowsiness, blurred vision, unsteady gait, dizziness, and vertigo; one participant discontinued after drowsiness and unsteady gait. | The protocol summarizes the study but does not provide a full volunteer-study report or establish long-term safety. | Early human safety observations |
| Phelan-McDermid phase 3 registration | Pediatric participants with Phelan-McDermid syndrome | Randomized, double-blind, placebo-controlled | Oral NNZ-2591 or placebo for 13 weeks | The registry has no posted results | Recruitment and status can change; registration is not efficacy evidence | Ongoing controlled trial |
Cautions
Safety and unknowns
- Most adverse events in the small Phelan-McDermid study were mild or moderate. One severe hyperactivity event was considered possibly related to NNZ-2591.
- The corrected table reported adverse events in 17 of 18 participants. One serious case of gastroenteritis occurred during follow-up and was considered unrelated to the drug.
- Three participants discontinued after adverse events, including one after seizures; investigators did not consider these events related to the study drug.
- A sponsor protocol summarizes an earlier study of 28 healthy adults. Events considered drug-related included drowsiness, blurred vision, unsteady gait, dizziness, and vertigo. One participant stopped after drowsiness and unsteady gait.
- The protocol identifies possible kidney injury, cataracts, and lens degeneration as concerns from rat toxicology. These potential risks are not established human harms; the volunteer-study summary reported no kidney findings.
- Longer-term safety and safety outside the studied population remain uncertain.
Product quality
Product identity and quality
The study used an oral formulation provided in a monitored clinical trial. A separately marketed product is not established as equivalent.
Compound name
NNZ-2591 and NNZ-2566 identify different compounds, not interchangeable product codes.
Trial formulation
The clinical study's measured dose and safety monitoring do not verify another product's contents.
Mechanism
How it is proposed to work
The compound was designed around an IGF-1-related molecule and is being investigated for effects relevant to nerve-cell signaling.
Proposed effects on IGF-1-related signaling and mouse behavior remain research hypotheses, not established clinical mechanisms.
Details
Technical details
Sources
References
- 1.
PubMed. NNZ-2591 in children and adolescents with Phelan-McDermid syndrome: phase 2 trial results
doi:10.1212/NXG.0000000000200338 PMID:41450730 NCT05025241
Single-group, open-label trial; the associated erratum corrects the safety table.
- 2.
PubMed. Erratum for the NNZ-2591 Phelan-McDermid phase 2 trial
doi:10.1212/NXG.0000000000200405 PMID:42325945
Corrects a safety-table heading and reproduces the corrected table.
- 3.
ClinicalTrials.gov. Placebo-controlled phase 3 study of NNZ-2591 in Phelan-McDermid syndrome
NCT07281079
Registry describes a recruiting randomized study without posted results.
- 4.
ClinicalTrials.gov. NNZ-2591 Phelan-McDermid phase 2 protocol and earlier safety summaries
NCT05025241
Sponsor protocol summarizes a Shank3b knockout mouse experiment and an earlier healthy-volunteer study; it is not a full report of those studies.
- 5.
ClinicalTrials.gov. NNZ-2591 Phelan-McDermid protocol safety summary
NCT05025241
Section 8.5 summarizes adverse events in 28 healthy volunteers and potential kidney and eye risks from rat toxicology.
- 6.
Other. Neuren investigational product pipeline
Sponsor identifies NNZ-2591 as an investigational agent, distinct from trofinetide.
- 7.
FDA. Drugs@FDA search page for ercanetide
An openFDA exact active-ingredient query for ercanetide found no match. The link opens the FDA search page, not a saved result; names and database coverage are limited.
- 8.
DailyMed. DAYBUE and DAYBUE STIX U.S. prescribing information
Trofinetide is the active ingredient of the approved Rett products; it is not NNZ-2591.