Inotrem, an advanced clinical stage biotech company specializing in immunotherapies for acute and chronic inflammatory syndromes, disclosed for the first time at the International Sepsis Forum held in Barcelona the results for its Phase IIb ASTONISH clinical trial in septic shock patients.
Article continues below
ASTONISH was designed to show the efficacy of nangibotide in septic shock with a precision medicine approach aiming to identify patients who benefit the most from this innovative treatment.
This global study enrolled 361 patients across 41 clinical sites in 6 European countries and the United States and succeeded in demonstrating a therapeutic benefit of nangibotide in patients with high levels of the TREM-1 pathway activation marker, soluble TREM-1 (sTREM-1).
ASTONISH studied as a primary endpoint the improvement in SOFA score, a well-established morbidity score evaluating patient clinical evolution and organ function.
The change of this score at 5 days after initiation of treatment in the nangibotide-treated arms was compared to the placebo arm in all patients and in patients with a high level of sTREM-1.
Importantly, and as part of the prespecified analysis for defining the optimal sTREM-1 cut-off, the benefit of nangibotide high dose treatment versus placebo was clinically and statistically significant at higher concentrations of sTREM-1, representing about 50% of the study population.
Consistent with prior preclinical, observational and Phase IIa trial data in this setting, ASTONISH confirmed that excessive TREM-1 activity is associated with severe immune dysregulation, organ dysfunction and ultimately death.
ASTONISH demonstrates that TREM-1 modulation with nangibotide improves respiratory, cardiovascular and renal function.
The study also provided evidence that nangibotide meaningfully impacts other relevant clinical parameters, displaying a trend towards improvement in All-Cause Mortality at day 28 and the proportion of patients Alive and free of organ support at day 28. ■