Inotrem has announced positive results for ESSENTIAL, its phase II clinical trial in COVID-19 patients hospitalized in critical care units and experiencing acute respiratory distress.
The French clinical stage biotech company specializes in immunotherapies for acute and chronic inflammatory syndromes. The announcement was made at the European Society of Intensive Care Medicine’s Annual Congress, held in Paris.
Study results
The ESSENTIAL study was terminated at 220 randomized ICU patients requiring ventilatory support (stage 5 or 6 on a 7-point clinical status ordinal scale) and compared infusion of nangibotide at 1mg/kg/hr for up to 5 days of treatment with standard of care. Despite a lower than anticipated sample size, the study met its primary endpoint of an improvement in clinical status according to 7-point clinical status ordinal scale from baseline to Day 28.
Nangibotide treatment also showed a statistically and clinically meaningful 12% absolute and 43% relative reduction in Day 28 mortality (key secondary endpoint) in the overall trial population. Among the subpopulation of patients with levels of the TREM-1 pathway activation marker, soluble TREM-1 (sTREM-1) above the median, the absolute and relative reduction in mortality was even more pronounced, amounting to 20% and 47%, respectively.
The study showed nangibotide has a significant and positive impact on the progression of the disease in patients receiving ventilatory support due to COVID-19, as well as on the severity of the respiratory failure, and length of stay in ICU. The trial showed sTREM-1 is an effective prognostic marker of outcome in severe COVID-19 and, consistent with the results from the company’s prior ASTONISH study, confirmed that sTREM-1 is a predictive marker of a positive response to the treatment by nangibotide.
Jean-Jacques Garaud, senior VP head of scientific and medical affairs at Inotrem said: “This new trial brings compelling evidence that the TREM-1 pathway plays a central role in major life-threatening immune dysregulations caused by severe infections, whether it is severe forms of COVID-19 or septic shock. This study strongly suggests that nangibotide, which targets TREM-1, is pathogen agnostic and has the potential to treat those very severe inflammatory conditions caused by both viral and bacterial infections.”
Sven Zimmermann, CEO of Inotrem, added: “We are grateful for the continued financial support and confidence awarded to us by the French public authorities to fight COVID-19. This attests of the relevance of our innovative approach to treat inflammatory diseases. The data we obtained is extremely encouraging, and we plan on quickly consulting regulatory authorities in the U.S. and EU.”
Support from public funding
At the start of the pandemic in 2020, Inotrem set out to build on the similarities between the immune dysregulation in severe forms of COVID-19 with those observed in septic shock patients. Inotrem launched ESSENTIAL, its clinical trial to assess the efficacy of its drug lead candidate, nangibotide, for COVID-19 patients in the ICU.
In July 2020, the CoviTREM-1 consortium, which includes the Nancy and Limoges university hospitals and Inotrem, obtained a first public funding of €7.5 million under a call for projects operated by the Secretary General for Investment and Bpifrance.
In December 2020, the trial was declared a Research National Priority by the French government. In July 2021, Inotrem was authorized to pursue the clinical development of nangibotide up to registration for COVID-19 patients and can draw on additional public funding of up to €45 million from Bpifrance, as part of the Programme d’Investments d’Avenir.