Nangibotide: what is known about the drug in septic shock?
Clinical review pending
Nangibotide is an experimental peptide aimed at runaway inflammation. Its phase 2b trial in septic shock missed its primary endpoint; efficacy is not established.
Whether nangibotide helps people with septic shock has not yet been shown. In ASTONISH, a controlled phase 2b trial, the experimental drug did not meet its prespecified main goal. Nangibotide is not approved.
What is nangibotide?
Nangibotide, also called LR12 or Motrem, is an experimental peptide made of twelve amino acids. It inhibits TREM-1, a receptor that amplifies inflammatory responses. The company Inotrem is developing the drug as a treatment for septic shock; it is given as an intravenous infusion, meaning into a vein.
In septic shock, an infection triggers a dangerous drop in blood pressure and impairs organ function. The condition is life-threatening. Nangibotide is still under clinical investigation for this use.
How does nangibotide work?
Nangibotide is intended to dampen the excessive inflammatory response in septic shock. It does this by interfering with the activation of TREM-1. The abbreviation stands for “Triggering Receptor Expressed on Myeloid cells-1”. This receptor amplifies the immune system’s inflammatory response, which can become harmful in septic shock. Nangibotide acts like a decoy: it blocks TREM-1 activation and is meant to reduce the release of pro-inflammatory signals. Whether this approach actually helps patients cannot be inferred from the mechanism alone. ASTONISH trial publication.
Soluble TREM-1 serves as a biomarker here, a measurable indicator of how active this pathway is. The marker is used to select patients in whom the TREM-1 pathway is especially strongly activated.
Is nangibotide FDA approved?
No. Nangibotide is not approved and is still under clinical investigation. Development has continued with a possible phase 3 trial in view. That trial is planned to select patients by biomarkers and so focus on a specific patient group.
What does the research show?
In ASTONISH, a controlled phase 2b trial, researchers tested whether nangibotide improves organ function in septic shock. As the primary endpoint, the prespecified main criterion, they used a score that rates organ failure. The trial did not meet this endpoint. ASTONISH trial publication.
| Patient group | Result on the organ-failure score |
|---|---|
| Prespecified group with high biomarker levels | The improvement was not statistically significant |
| Entire study population | The improvement was not statistically significant |
| Only at higher biomarker cutoffs | An improvement described as clinically relevant; this subgroup finding has not yet been confirmed |
The company had earlier presented the result as positive. In the peer-reviewed publication, however, the authors state that the trial did not meet its primary endpoint. Nor does the still unconfirmed subgroup finding establish that nangibotide works.