Investigator-sponsored FORCE trial did not meet primary endpoints
Company will stop exploring avdoralimab in COVID-19
Investigator-sponsored avdoralimab clinical trial in inflammation will continue
Innate Pharma SA (Euronext Paris: IPH – ISIN: FR0010331421; Nasdaq: IPHA) (“Innate” or the “Company”) today announced that FORCE (FOR COVID-19 Elimination), the investigator-sponsored, Phase 2 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 Joyson Karakunnel, MD, MSc, FACP, Chief Medical Officer of Innate Pharma. “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 Julien Carvelli, MD, ICU, Timone Hospital, AP-HM, investigator of the FORCE clinical trial. “We are grateful to the patients and their families who supported the FORCE trial and contributed to the global fight against this disease.”
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.
Based on these results, the Company will stop exploring avdoralimab in COVID-19. Today’s results do not impact the investigator-sponsored, Phase 2 trial of avdoralimab in bullous pemphigoid, an inflammatory disease, which is currently enrolling patients. More than 100 patients have been treated with avdoralimab in inflammation and oncology clinical trials with no new or unexpected safety signals observed.
About the FORCE clinical trial:
FORCE is a multi-center, randomized, double-blind, placebo-controlled Phase 2 trial evaluating avdoralimab in COVID-19 patients with severe pneumonia. The trial is sponsored by Assistance Publique–Hôpitaux de Marseille.
The trial enrolled a total of 208 patients (age 18-80) between the three cohorts:
- Cohort 1: evaluated patients with severe pneumonia without Acute Respiratory Disease Syndrome (ARDS) at baseline. The primary endpoint was clinical improvement on the WHO scale at D14 and D28.
- Cohort 2: evaluated patients with severe pneumonia complicated by ARDS and admitted into the ICU at baseline. The primary endpoint was the number of days without mechanical ventilation at D28.
- Cohort 3: evaluated patients with COVID-19-related ARDS requiring mechanical ventilation. The primary endpoint was clinical improvement on the WHO scale at D14 and D28
The trial was launched based on findings from the Marseille-based exploratory research taskforce, named EXPLORE COVID-19, which analyzed immune cells in COVID-19 patients at different stages of the disease. Results from this translational study were published in Nature.
In August 2020, the Company announced it obtained up to €6.8 million in public funding from the French government for its COVID-19 R&D activities. This funding is part of the government’s PSPC COVID call for COVID-19 related projects and will cover the Company’s development of its COVID-19 activities, which began in March 2020, including the EXPLORE COVID-19 translational research study and its two Phase 2 investigator-sponsored clinical trials, FORCE and ImmunONCOVID-20.
Avdoralimab (IPH5401) is a therapeutic antibody that specifically binds and blocks C5a receptors (C5aR1) expressed on subsets of myeloid-derived suppressor cells (MDSC) and neutrophils. Targeting C5a/C5aR1 has been demonstrated scientifically and through positive clinical trials in some complement-driven inflammatory diseases.