Inotrem looks to regulatory agencies after COVID treatment hits phase 2 goals

Though many COVID-19 treatments are in development, few have yet to cross the approval threshold in the U.S. or Europe. French biotech Inotrem hopes to change that, posting phase 2 data that show its only clinical-stage compound could help critically ill COVID patients.

The data, released today at the European Society of Intensive Care Medicine’s annual congress in Paris, comes from Inotrem’s trial dubbed ESSENTIAL. The phase 2 study evaluated Inotrem’s nangibotide, a peptide designed to inhibit TREM-1—which are receptors on certain white blood cells—among ventilated COVID-19 patients in the ICU.

The study was funded by the French government and enrolled 220 patients, deviating from initial plans to enroll 730 participants.

"The study was initially designed as a phase 2/3 registration trial with a total target of more than 700 patients,” Inotrem CEO Sven Zimmermann told Fierce Biotech via email. “However, after the sharp decline in critically ill, severe COVID-19 patients in ICUs across Europe earlier this year, Inotrem took the decision to stop after 220 enrolled patients to read out the data.”

Investigators looked to see how patients receiving 1-mg infusions of nangibotide every hour for up to five days fared versus those receiving standard of care. They used a seven-point ordinal scale to assess clinical status, with data showing improved status from baseline to the 28th day of treatment for severe COVID-19 patients and hitting the trial’s main goal.

The data also demonstrated a statistically significant 12% absolute and 43% relative reduction in mortality on Day 28. The observed effect size in terms of absolute reduction in mortality at Day 28 of the initial 220 patients was more pronounced than anticipated, according to Zimmermann.

Overall, the study found that nangibotide had a significant and positive impact on disease progression, severity of respiratory failure and length of ICU stay, according to an Oct. 25 release.

The data drop is the second in a small string of promising news for Inotrem, following a separate phase 2b readout by only a few weeks. That trial assessed nangibotide among septic shock patients, sparking hope as it hit its main goal of improving patient scores on an organ failure assessment scale. In 2019, the peptide received fast-track designation from the FDA for septic shock and holds a similar status from the European Medical Association. 

“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,” Jean-Jacques Garaud, M.D., Inotrem’s senior vice president and head of scientific and medical affairs, said in the release. “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.”

Inotrem leaders now plan to consult both U.S. and EU regulatory authorities about getting the treatment out to patients with severe COVID-19.