A proof-of-concept trial led by the Universities of Birmingham and University Hospitals Birmingham NHS Foundation Trust has identified a drug that may offer benefit some patients hospitalized with COVID-19 pneumonia.

The CATALYST trial tested UK-based biopharmaceutical company Izana Bioscience’s namilumab (IZN-101) as a potential therapeutic to treat patients who are hospitalized with COVID-19 pneumonia, and receiving usual care, as well as having high levels in their blood of a marker of inflammation known as C-reactive protein (CRP). CRP levels rise when there is inflammation in the body, and elevated levels of CRP have been found to be a potential early marker to predict risk for severity of COVID-19.

An antibody already in late-stage trials to treat rheumatoid arthritis, namilumab targets a cytokine which is naturally secreted by immune cells in the body but, in uncontrolled levels, is believed to be a key driver of the excessive and dangerous lung inflammation seen in COVID-19 patients.

The trial, carried out in collaboration with the University of Oxford and funded by the Medical Research Council and carried out between June 2020 and February 2021, involved patients aged over 16 with COVID-19 pneumonia either being treated on a ward or intensive care unit (ICU) at nine NHS hospitals across the UK.

The study, published in The Lancet Respiratory Medicine, involved 54 patients receiving usual care (steroids and oxygen or ventilation, depending on the severity of disease) and 57 patients given usual care as well as a single intravenous dose of 150mg of namilumab.

As well as COVID-19 pneumonia, all study participants had CRP levels greater than 40mg/l. The researchers compared the probability of the reduction of levels of CRP in patients. Compared to usual care alone, the researchers found there was a 97% probability of CRP being reduced over time in those given namilumab when compared with usual care alone.

The patients were monitored, and after 28 days the study also showed there were fewer deaths and more discharges from hospital or ICU in those who had been given namilumab compared to those receiving usual care alone.

By day 28, 78% (43) of the patients receiving namilumab were discharged from hospital or ICU, compared to 61% (33) of the patients given usual care. In the namilumab group, 11% (6) were still in the hospital by day 28, compared to 20% (11) in the usual care group. Of those in the namilumab group, 11% (6) patients died compared to 19% (10) who died in the usual care group by day 28.

The team calculated the differences between the two cohorts in the overall probability of those being discharged from ICU or a ward at 28 days. Of those on a ward, the probability of discharge at day 28 was 64% in the usual care cohort, compared to 77% in the Namilumab cohort. Of those in ICU, probability of discharge at day 28 was 47% in the usual care group, compared to 66% in the Namilumab cohort.

“Our research has provided important proof-of-concept evidence that namilumab reduces inflammation in hospitalized patients with COVID-19 pneumonia.  However, our sample size is too small for a definitive assessment of clinical outcomes and further studies are required for this, as well as to understand better the population that may benefit most,” says Ben Fisher, MD, co-chief investigator of the CATALYST trial at the University of Birmingham’s Institute of Inflammation and Ageing.

“Our results may not generalize to hospitalized patients without evidence of pneumonia or raised CRP or patients not requiring hospitalization. It is important, therefore, that namilumab is now prioritized for further COVID-19 research in a much larger national Phase III clinical trial.”