Nangibotide: evidence, FDA status and research

It is a drug being tested for septic shock, a life-threatening reaction to infection. One trial of 355 patients missed its main goal, with a hint of benefit in some patients.

Sold for

Nangibotide is discussed as a possible first targeted immune therapy for septic shock, a condition where nearly every drug tried has failed.

Studies say

A single controlled trial missed its primary endpoint, with a post hoc hint of benefit in patients with high soluble TREM-1 levels, which is enough for B but not for a claim that it works.

Why grade B. One randomized, double-blind, placebo-controlled phase 2b trial in 355 patients with septic shock exists. It did not meet its primary endpoint, and the encouraging signal came from an exploratory analysis in patients with higher biomarker levels. A confirmatory trial is what is missing. ¹

FDA. Not approved by the FDA for any use. Nangibotide is an investigational drug for septic shock; a phase 2b trial has been published, and its authors say a further trial is needed to confirm any benefit. ¹

Written from 1 cited sources. Fact-checked 2026-10-27: 10 claims checked, 1 corrected. Last refreshed 2026-10-27. Not physician reviewed.

What this means for you

What people take it for: Septic shock
Can a US doctor prescribe it?: Not yet; it is still in trials.
Properly tested in people?: Partly: one trial of 355 patients that missed its main goal.

Evidence checklist

Randomised controlled trial ASTONISH, double-blind phase 2byes
Human study over 100 people ASTONISH, 355 septic shock patientsyes
More than one research group Single trial from the sponsorno
Clinical outcomes, not surrogate markers Missed organ-failure score endpoint; no mortality datano
Human safety data beyond case reports One infusion course studied onlyno

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

What it is

Nangibotide is a short synthetic peptide developed by the French company Inotrem for septic shock, the stage of sepsis where blood pressure collapses and organs begin to fail. It is given as a continuous intravenous infusion in intensive care. It has no use outside hospital settings and is not sold as a research chemical. ¹

The drug targets TREM-1, a receptor on immune cells that amplifies inflammation. The idea is to calm an overshooting immune response without shutting it off completely, which earlier anti-inflammatory approaches in sepsis failed to do. ¹

How it works

TREM-1 (triggering receptor expressed on myeloid cells 1) sits on neutrophils and monocytes and is an amplifier: when other sensors detect infection, TREM-1 boosts the release of inflammatory signals. In sepsis this amplification runs out of control. Nangibotide is a decoy: a fragment of a TREM-1-related protein that binds the receptor's ligand so the amplification loop is damped. The amount of soluble TREM-1 in a patient's blood is a marker of how active this pathway is, which is why the trial tested the drug separately in patients with high levels. ¹

What human research shows

The ASTONISH trial randomized 355 adults with septic shock to a low dose of nangibotide, a high dose, or placebo, on top of standard care. The primary outcome was the change in the SOFA organ failure score from baseline to day 5, assessed both in the whole population and in the pre-specified group with soluble TREM-1 at or above a set threshold. The trial did not meet that primary endpoint. ¹

In an analysis of the biomarker threshold, patients with higher soluble TREM-1 levels than the pre-specified cutoff appeared to gain a clinically relevant SOFA improvement on the high dose compared with placebo, and the low dose showed a smaller effect in the same direction. The authors say this needs confirmation in a future study, since the cutoff that showed benefit was identified after the fact. ¹

Study	Model	Finding
ASTONISH phase 2b	Humans, n=355 with septic shock, randomized double-blind placebo-controlled	No significant improvement in SOFA score at day 5 in the pre-specified groups; a post hoc analysis suggested benefit at higher soluble TREM-1 cutoffs. ¹
ASTONISH biomarker cutoff analysis	Humans, subgroup of the 355-patient trial with higher baseline soluble TREM-1	High-dose nangibotide was associated with a SOFA improvement of two points or more versus placebo at cutoffs above the pre-specified threshold, an exploratory result the authors say needs confirmation. ¹

Safety

In ASTONISH, the adverse event profile was similar between nangibotide and placebo, which matters because septic shock patients are already very sick and extra harm would have been easy to miss. Mortality was not the primary endpoint and the trial was not powered to detect a difference in deaths. Safety beyond a single infusion course, and in people who are not in septic shock, has not been studied. ¹

Questions for your clinician

Is nangibotide available only through a trial, and am I eligible?
The benefit appeared in a subgroup; has it been confirmed in a new trial?
What standard sepsis care should I expect regardless?

Questions people ask

Does nangibotide reduce deaths from sepsis?

Unknown. The published trial measured organ failure scores, not survival, as its main outcome, and it did not meet that endpoint. A larger trial would be needed to answer the mortality question. ¹

Why test the drug only in patients with high soluble TREM-1?

Soluble TREM-1 in the blood indicates how strongly the pathway the drug blocks is activated. The trial's logic was that patients with low activation have little for the drug to act on, so benefit should be concentrated in those with high levels. The data were consistent with that idea but did not prove it. ¹

Can I buy nangibotide?

It is an intravenous hospital drug in clinical development and is not available through pharmacies or as a research chemical. It has no plausible use outside intensive care. ¹

Citations

François 2023, Lancet Respir Med: nangibotide in patients with septic shock (ASTONISH), randomized phase 2b trial doi.org