Topline results were announced from a phase 3 trial evaluating the efficacy and safety of a single dose of abatacept or infliximab in adults hospitalized with moderate to severe COVID-19.
The randomized, placebo-controlled phase 3 ACTIV-1 Immune Modulators trial (ClinicalTrials.gov Identifier: NCT04593940) was led by the National Institutes of Health (NIH) and enrolled 1971 hospitalized adults with moderate to severe COVID-19. The trial assessed 3 immunomodulating agents: abatacept (Orencia), a selective T cell costimulation modulator; infliximab (Remicade), a tumor necrosis factor blocker; and cenicriviroc, an investigational immunomodulator that blocks 2 chemokine receptors, CCR2 and CCR5.
Patients were randomly assigned to receive a single dose of abatacept 10mg/kg intravenously (IV), infliximab 5mg/kg IV, or placebo as an add-on treatment to standard of care (about 90% received remdesivir and 85% received dexamethasone).
Results showed that while not statistically significant, abatacept and infliximab were both associated with a strong improvement in the primary endpoint of time to recovery, as measured by day of hospital discharge, compared with placebo. Both treatments reduced the risk of death and led to improvements in clinical status.
Among the 509 participants who received abatacept, the death rate was 11% vs 15% for the placebo group (n=513), corresponding to a 37.4% reduction in the odds of dying. Patients in the abatacept arm also had 34.2% better odds of clinical improvement compared with the placebo arm.
Among the 518 participants who received infliximab, the death rate was 10% vs 14.5% for the placebo group (n=519), corresponding to a 40.5% reduction in the odds of dying. Patients in the infliximab arm also had 43.8% better odds of clinical improvement compared with the placebo arm.
“When given in addition to standard of care treatments, like remdesivir and dexamethasone, infliximab and abatacept each offered a substantial reduction in mortality,” said the trial’s protocol chair, William G. Powderly, MD, director of the Institute for Clinical and Translational Sciences and co-director of the Division of Infectious Diseases at Washington University School of Medicine in St. Louis. “These drugs could potentially add to the therapeutic options available for the treatment of patients hospitalized with COVID-19.”
Administration of the investigational treatment cenicriviroc was stopped in September 2021 after an independent data and safety monitoring board recommended discontinuing the sub-study due to lack of efficacy.
- Immune modulator drugs improved survival for people hospitalized with COVID-19. News release. National Institutes of Health. Accessed June 2, 2022. https://www.nih.gov/news-events/news-releases/immune-modulator-drugs-improved-survival-people-hospitalized-covid-19
- Bristol Myers Squibb announces topline results showing treatment with Orencia (abatacept) improved survival in people hospitalized with COVID-19. News release. Bristol Myers Squibb. Accessed June 2, 2022. https://www.businesswire.com/news/home/20220601006299/en/Bristol-Myers-Squibb-Announces-Topline-Results-Showing-Treatment-with-Orencia-abatacept-Improved-Survival-in-People-Hospitalized-with-COVID-19