Rheumatoid Arthritis Drug Could More Effectively Treat Patients Hospitalized With COVID-19 Pneumonia

A proof-of-concept study has identified a drug that may provide benefits to some patients hospitalized with COVID-19 pneumonia.

A proof-of-concept study led by the Universities of Birmingham and the University Hospitals Birmingham NHS Foundation Trust has identified a drug that may provide benefits to 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 agent for the treatment of patients hospitalized with COVID-19 pneumonia receiving ‘regular’ care, as well as high levels in their blood of an inflammatory marker known as C-reactive protein (CRP). CRP levels rise when there is inflammation in the body, and elevated levels of CRP appear to be a potential early marker to predict the risk of COVID-19 severity.

Namilumab, an antibody that is already in late-stage studies for the treatment of rheumatoid arthritis, targets a ‘cytokine’ that is naturally secreted by immune cells in the body, but in uncontrolled levels it is believed to be a major cause is from the excessive and dangerous pneumonia seen in COVID-19 patients.

The trial, conducted in partnership with the University of Oxford and funded by the Medical Research Council and conducted between June 2020 and February 2021, involved patients over 16 years of age with COVID-19 pneumonia who were either admitted to a ward or intensive care unit. treated (ICU) in nine NHS hospitals in the UK.

The study, published Dec. 16, 2021 in The Lancet Respiratory Medicine, involved 54 patients who received “regular care” (steroids and oxygen or ventilation, depending on the severity of the disease) and 57 patients who received usual care, as well as a single 150 mg intravenous dose of namilumab.

In addition to COVID-19 pneumonia, all study participants had CRP levels greater than 40 mg/L. The researchers compared the chance of a reduction in CRP levels in patients. Compared with usual care alone, the researchers found that there was a 97% chance that CRP was reduced over time in those who received namilumab compared with usual care alone.

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

At Day 28, 78% (43) of patients receiving namilumab had been discharged from the hospital or ICU compared to 61% (33) of patients receiving usual care. In the namilumab group, 11% (6) were still in hospital at Day 28, compared to 20% (11) in the usual care group. Of those in the namilumab group, 11% (6) of patients died on Day 28 compared to 19% (10) who died in the usual care group.

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

dr. Ben Fisher, co-principal investigator of the CATALYST study at the University of Birmingham’s Institute of Inflammation and Aging, and consultant rheumatologist at the University Hospitals Birmingham NHS Foundation Trust (UHB), said: “Our study has provided important evidence 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 requires further studies, as well as to better understand the population that will benefit most from it. Our results cannot be generalized to hospitalized patients without evidence of pneumonia or elevated CRP or patients who do not require hospitalization, so it is important that namilumab is now prioritized for further COVID-19 research in a much larger national Phase III clinical trial. ”

dr. Someit Sidhu, co-founder of Izana Bioscience, said: “We are proud to support the CATALYST study led by the highly experienced team from the University of Birmingham and UHB, Europe’s largest integrated center for intensive care. “We believe that namilumab can play an important role in reducing hyperinflammation seen in patients with severe COVID-19 infection and are committed to working with regulators and partners around the world to ensure these potential therapy can be developed for patients with COVID-19. who need urgent treatment. This is a particularly important moment for me as I support the global response to this pandemic through the work of the team at University Hospital Birmingham – the hospital where I trained as a physician assistant before founding Izana.”

The CATALYST team also tested a second drug called infliximab (CT-P13), which is currently used as a treatment for inflammatory conditions. They compared the same patients with COVID-19 pneumonia and CRP levels above 40 mg/l who received ‘usual care’ with 35 patients who received usual care and a single intravenous dose of 5 mg/kg infliximab. However, the study found that infliximab was no more effective than usual care, with only a 15% chance of lowering CRP.

dr. Fisher added: “Our findings regarding infliximab, while disappointing, are also important as we continue to explore and identify existing and new anti-inflammatory drugs that could play a critical role in addressing and reducing the most severe symptoms of COVID-19. 19. .”

Reference: “Namilumab or infliximab compared to standard of care in hospitalized patients with COVID-19 (CATALYST): a randomized, multicenter, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept study” by Benjamin A Fisher, MD[Res]; Prof Tonny Veenith, PhD; Daniel Slade, MSc; Charlotte Gaskell, MSc; Matthew Rowland, DPhil; Prof Tony Whitehouse, MD; James Scriven, PhD; Dhruv Parekh, PhD; Madhu S Balasubramaniam, MBBS; Prof Graham Cooke, DPhil; Nick Morley, MBBS; Zoe Gabriel, MBBS; Matthew P Wise, DPhil; Prof Joanna Porter, PhD; Prof Helen McShane, PhD; Prof Ling-Pei Ho, DPhil; Prof Philip N Newsome, PhD; Anna Rowe, PhD; Rowena Sharpe, PhD; Prof David R Thickett, DM; Prof Julian Bion, MD; Prof Simon Gates, PhD; Prof Duncan Richards, DM and Prof Pamela Kearns, PhD on behalf of the CATALYST investigators, Dec 16, 2021, The Lancet Respiratory Medicine.
DOI: 10.116/S2213-2600(21)00460-4

CATALYST was designed by the Inflammation – Advanced and Cell Therapy Trials Team (I-ACT) of the Cancer Research UK Clinical Trials Unit at the University of Birmingham and is managed in close collaboration with UHB and the Birmingham National Institute for Health Research Biomedical Research Centers (NIHR). BRC) and delivered in close collaboration with the NIHR BRCs at Oxford, Imperial College London and University College London.