Peptide education
Nangibotide
LR12
Nangibotide is an investigational peptide studied in intensive care for septic shock. It is intended to inhibit TREM-1, a receptor involved in amplifying inflammation.
The larger phase 2b trial did not meet its primary organ-failure endpoint. A separate, early-stopped COVID-19 trial reported a clinical-status signal that did not meet its adjusted significance threshold.
Overview
Quick answer
A biological target and a favorable finding in an exploratory subgroup are not the same as a successful prespecified clinical trial endpoint.
What was it studied for?
Researchers tested intravenous nangibotide in adults with septic shock receiving intensive care. It has not been established as effective for this condition by the trials described here.
Did the larger trial succeed?
No. Neither dose achieved the prespecified primary organ-failure outcome in the overall or predefined high-biomarker group. A higher threshold produced an exploratory signal that needs confirmation.
Is it an FDA-approved treatment?
An editorial search for the full name nangibotide found no matching Drugs@FDA application. The linked FDA overview leads to the search but is not a saved result; coverage and alternative names limit the finding.
Evidence
Evidence snapshot
Neither tested infusion rate significantly improved the prespecified SOFA comparison.
A higher sTREM-1 threshold was associated with a signal that needs an independent confirmatory study.
The phase 2a trial focused on safety; the registry reports 50 randomized and 49 treated, while the paper's abstract says 49 were randomized.
The ordinal clinical-status comparison did not meet the significance threshold adjusted for early stopping.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Nangibotide has been proven to treat septic shock. | The phase 2b trial did not meet its prespecified primary organ-failure endpoint. | The peptide was designed to inhibit the TREM-1 inflammatory pathway. | The mechanism and an exploratory subgroup signal do not establish treatment efficacy. |
| Similar adverse-event rates prove it is safe. | In the phase 2b trial, adverse-event frequencies were similar across the three groups. | Similar observed rates do not rule out rare effects or establish safety in other populations. |
Bottom line
Main takeaway
This is an experimental critical-care drug and its benefit is not established.
Septic shock is a medical emergency requiring hospital care.
Keep the prespecified biomarker cutoff separate from the exploratory higher-threshold analysis.
Identity
What it is
Nangibotide is also known as LR12 and has been studied as a TREM-1 inhibitor.
Research
Research evidence
An initial safety-focused randomized study was followed by ASTONISH, a larger placebo-controlled trial. The latter did not meet its primary comparison, despite an exploratory result at a higher biomarker cutoff. A separate COVID-19 study stopped early; its clinical-status comparison did not meet the adjusted significance threshold and needs confirmation.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| ASTONISH | 355 patients in the main septic-shock analysis | Randomized, double-blind, placebo-controlled phase 2b trial | Two intravenous nangibotide infusion rates versus placebo | Neither dose met the prespecified primary SOFA-score comparison in the overall or predefined high-biomarker population. | The higher sTREM-1 threshold with a favorable signal was exploratory and needs confirmation. | Randomized trial with a negative primary endpoint |
| Phase 2a safety study | 50 randomized patients with septic shock in the registry; 49 received study treatment | Randomized, double-blind, placebo-controlled study | Three continuous intravenous infusion rates | Treatment-emergent adverse events were not significantly different; exploratory SOFA comparisons were not significant. | The paper's abstract says 49 were randomized, while the registry reports 50; small groups limit assessment of rare harms and clinical efficacy. | Early safety-focused randomized study |
| ESSENTIAL | 219 analyzed adults with COVID-19 receiving respiratory support | Randomized, double-blind, placebo-controlled phase 2 trial | Nangibotide versus placebo in critically ill patients | The primary ordinal clinical-status comparison reported p = 0.04 but did not meet the early-stop-adjusted significance threshold. In a planned binary sensitivity analysis, 77 of 119 nangibotide recipients and 52 of 100 placebo recipients improved by day 28. | The study stopped early for low recruitment; the binary result is a sensitivity analysis and the findings need confirmation. It was not a septic-shock trial. | Early-stopped randomized trial with an unconfirmed clinical-status signal |
Use context
Reported use context
These are supervised intensive-care research protocols, not directions for use.
Study and label context
After a loading infusion, the study used maintenance rates of 0.3 or 1.0 mg/kg per hour. Treatment was planned for at least about 3 days and at most about 5 days, depending on vasopressor use.
The published and filed protocols express loading units differently, so the loading amounts are not reported here. This was not an established treatment regimen.Infusion rates of 0.3, 1.0, or 3.0 mg/kg per hour were studied for up to 5 days.
This small safety-oriented study cannot establish an effective dose.Cautions
Safety and unknowns
- Adverse events were common in all groups of the phase 2b trial, reflecting a critically ill population.
- Similar observed rates do not exclude rare or delayed drug-related harms.
- Effects outside the studied intensive-care populations are not established.
Product quality
Product identity and quality
A trial preparation cannot verify the identity or sterility of a separate product.
Identity
A shared peptide name does not verify a product's contents.
Sterility
Intravenous administration carries serious product-quality risks.
Mechanism
How it is proposed to work
The drug was designed to reduce signaling through TREM-1, which can amplify inflammation.
Soluble TREM-1 was investigated as a biomarker for selecting patients, but the higher-cutoff finding remains exploratory.
Details
Technical details
Sources
References
- 1.
PubMed. Nangibotide in septic shock: phase 2a randomized trial
doi:10.1007/s00134-020-06109-z PMID:32468087
Safety-focused randomized study with exploratory efficacy outcomes; the abstract reports 49 randomized.
- 2.
Other. Nangibotide phase 2a trial registry results
NCT03158948
The EU registry reports 50 randomized and 49 treated; one patient died before treatment.
- 3.
PubMed. ASTONISH phase 2b trial of nangibotide in septic shock
doi:10.1016/S2213-2600(23)00158-3 PMID:37269870 NCT04055909
The prespecified primary organ-failure endpoint was not met; higher biomarker thresholds were exploratory.
- 4.
Other. ASTONISH phase 2b trial protocol
doi:10.1136/bmjopen-2020-042921 NCT04055909
Open-access copy of the published protocol; its loading units differ from the filed protocol.
- 5.
ClinicalTrials.gov. ASTONISH study protocol filed with ClinicalTrials.gov
NCT04055909
The filed protocol describes loading rates over 15 minutes; the published protocol uses different units for the same numbers.
- 6.
PubMed. ESSENTIAL trial of nangibotide in COVID-19 respiratory failure
doi:10.1016/j.eclinm.2023.102013 PMID:37350989 NCT04429334
Randomized phase 2 COVID-19 study stopped early; the full report describes its adjusted significance threshold and sensitivity analysis.
- 7.
FDA. FDA Drugs@FDA database scope and nangibotide search
An editorial search of the openFDA Drugs@FDA active-ingredient field for the full name nangibotide returned no match. The FDA overview links to the search but is not a saved result; alternate names and indexing limit the finding.