GSK announces results for its monoclonal antibody, otilimab, for the treatment of hospitalised adult patients with COVID-19.

GlaxoSmithKline plc announced results from the phase II proof of concept OSCAR (Otilimabin Severe COVID-19 Related Disease) study with otilimab, an investigational anti-granulocyte macrophage colony-stimulating factor (anti-GM-CSF) monoclonal antibody .The primary endpoint of the OSCAR study was the proportion of COVID-19 patients who were alive and free of respiratory failure 28 days after treatment with a single dose of otilimab in addition to standard of care (including anti-viral treatments and corticosteroids), compared to patients being treated with standard of care alone. Data from patients of all ages showed a treatment difference of 5.3% (95% CI= -0.8%, 11.4%) but this did not reach statistical significance. However, a pre-planned efficacy analysis by age in patients 70 years and older (N=180, 806 in total study) showed that 65.1% of patients were alive and free of respiratory failure 28 days after treatment with otilimab plus standard of care, compared to 45.9% of patients who received the standard of care alone (delta of 19.1%, 95% CI=5.2%, 33.1%) (nominal p-value=0.009). In addition, in a mortality analysis up to day 60, a treatment difference of 14.4% favouring otilimab was seen with rates of 40.4% on standard of care vs. 26% on otilimab plus standard of care (95% CI= 0.9%, 27.9%) (nominal p-value=0.040) in patients 70 years and older. Given these data suggest a potentially important clinical benefit in a pre-defined sub-group of high-risk patients and the public health need, GSK has decided to amend the OSCAR study to expand this cohort to confirm these potentially significant findings. Approximately 10-15% of patients diagnosed with COVID-19 experience severe disease involving respiratory problems that can require hospitalisation and intensive care, with an additional 5% of patients becoming critically ill. Age is widely recognised as a significant risk factor for severe COVID-19 disease. Greater disease severity and increased mortality are consistently observed in older patients with severe pulmonary COVID-19. According to the United States’ Centers for Disease Control and Prevention, the risk of hospitalisation is 5-times greater for patients age 70 to 74, rising to 8-times higher for patients age 75 and older. These patients often need breathing interventions including significant oxygen support or mechanical ventilation. The severe respiratory symptoms of COVID-19 are caused by the body’s immune system going into overdrive to eliminate the virus and can lead to life-threatening complications or even death. Recent research suggests the role of the cytokine GM-CSF in the immune response to COVID-19 may be more prominent in patients over the age of 70, putting them at an increased risk for serious complications related to COVID-19. There is an unmet need for additional therapeutics to help mediate the immune response in this patient population. The additional cohort of the OSCAR study will follow a similar study design and will enrol approximately 350 patients aged 70 years and older. Currently available therapies have limited clinical benefit in the more severe stages of hospitalised COVID-19 when patients require high-flow oxygen or invasive mechanical ventilation. To date, no targeted immunomodulatory therapy has been proven to have sufficient benefit in improving recovery from respiratory failure or reducing mortality in patients aged 70 years and older. In the OSCAR study, the most common serious adverse event observed was respiratory failure (5% for placebo, 4% for otilimab). Overall, all adverse events and serious adverse events observed were typical for a severe COVID-19 population. In the 70 years and older sub-group, the incidence rates of SAEs and fatal SAEs were lower in the otilimab group compared with the placebo group.