Avdoralimab Phase II FORCE trial in COVID-19 misses endpoints

French oncology-focused biotech Innate Pharma (Euronext Paris: IPH) saw its shares fall more than 4% to 2.94 euros by midday, having dropped as much as 8%, after it said it would stop exploring its avdoralimab in COVID-19.

The decision comes as Marseille-based Innate announced that FORCE (FOR Covid Elimination), the investigator-sponsored, Phase II clinical trial evaluating the safety and efficacy of its anti-C5aR1 antibody, avdoralimab, in COVID-19 patients with severe pneumonia, did not meet its primary endpoints in all three cohorts of the trial.

The FORCE trial was initiated based on pre-clinical data showing that patients who progress towards severe COVID-19 disease exhibit an activation of the C5a/C5aR1 pathway. These translational data were observed in the trial; however, they did not translate into clinical benefit over best supportive care.

“The FORCE trial was an opportunistic endeavor to help patients with severe COVID-19, and was  supported by pre-clinical data showing the importance of the C5aR1 pathway in the escalation of disease,” said Dr Joyson Karakunnel, chief medical officer of Innate, adding: “While we are disappointed with the results, these data contribute to the scientific understanding of the inflammatory pathways in this disease and potential avenues for treatment. We are proud of our partnership with Assistance Publique–Hôpitaux de Marseille (AP-HM) in this effort.”
 
“COVID-19-related severe pneumonia has been difficult to treat effectively, and stopping the escalation of disease is crucial to our patients,” said Dr Julien Carvelli, of the Timone Hospital, AP-HM, and chief investigator of the FORCE clinical trial.

Investigators and the Independent Data Monitoring Committee observed slightly higher deaths in the treatment arm compared to placebo without causality being established. Results from this trial, including translational data, are planned to be submitted for publication.