A proof-of-concept trial headed by British experts has found a drug that may offer benefit to some patients hospitalized with COVID-19 pneumonia.
The CATALYST trial evaluated namilumab (IZN-101), a drug developed by the UK-based biopharmaceutical company Izana Bioscience, as a potential treatment for COVID-19 patients who were receiving ‘standard’ therapy but had high levels of C reactive protein (CRP) in their blood. CRP levels rise when the body is inflamed, and elevated CRP levels have been discovered to be a potential early marker for COVID-19 severity risk.
Namilumab is an antibody that targets a cytokine released by immune cells in the body but is thought to be a primary driver of the excessive and severe lung inflammation seen in COVID-19 patients. It is already in late-stage trials to treat rheumatoid arthritis.
The trial, conducted in partnership with the University of Oxford and sponsored by the Medical Research Council, involved patients over the age of 16 with COVID-19 pneumonia being treated on a ward or in the Intensive Care Unit (ICU) at nine NHS hospitals across the UK between June 2020 and February 2021.
The trial included 54 patients who received “usual therapy” (steroids and oxygen or ventilation depending on disease severity) and 57 patients who received “usual care” plus a single intravenous dose of 150mg of namilumab.
All research subjects had CRP levels greater than 40mg/l, in addition to COVID-19. The researchers compared the likelihood of CRP levels in patients decreasing. When compared to conventional care alone, the researchers discovered that people who were given namilumab had a 97 percent chance of having their CRP reduced over time.
The patients were observed, and after 28 days, the study found that those who received namilumab had fewer deaths and more discharges from the hospital or ICU than those who received only standard treatment.
By day 28, 78 percent (43) of patients receiving namilumab had been discharged from the hospital or ICU, compared to 61 percent (33) of patients getting standard care. On day 28, 11 percent (6) of the namilumab group remained in the hospital, compared to 20 percent (11) in the standard care group. By day 28, 11 percent (6) of those in the namilumab group had died, compared to 19 percent (10) in the standard care group.
The researchers calculated the differences between the two cohorts in the overall likelihood of being discharged from ICU or a ward after 28 days. The probability of discharge from a ward on day 28 was 64% in the standard care cohort and 77 percent in the Namilumab cohort. The probability of release from the ICU on day 28 was 47 percent in the usual care group and 66 percent in the Namilumab cohort.
On study limitations, Dr. Ben Fisher, co-chief investigator said: “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. Our results may not generalise to hospitalised patients without evidence of pneumonia or raised CRP or patients not requiring hospitalisation. It is important, therefore, that namilumab is now prioritised for further COVID-19 research in a much larger national Phase III clinical trial.”
Dr. Someit Sidhu added: “We believe namilumab can play a significant role in dampening the hyper-inflammation seen in patients with severe COVID-19 infection and are committed to working with regulators and partners across the world to ensure this potential therapy can be developed for patients with COVID-19 who urgently need treatments.”
The CATALYST researchers also evaluated a second medicine, infliximab (CT-P13), which is presently used to treat inflammatory diseases. They compared 35 patients with COVID-19 pneumonia and CRP levels greater than 40mg/l who received ‘usual care’ to the same patients who received ‘usual care’ and a single intravenous dosage of 5mg/kg of infliximab. However, the study discovered that infliximab was no more effective than standard therapy, with just a 15 percent chance of lowering CRP.
Dr Fisher added: “Our findings relating to infliximab, while disappointing, are also important as we continue to investigate and identify existing and new anti-inflammatory drugs that may play a critical role in targeting and reducing the most serious symptoms of COVID-19.”
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