In a new study, researchers showed that the lymphoma drug acalabrutinib may offer a new treatment for severe COVID-19 infection.
The mechanisms of action of acalabrutinib led to the hypothesis it might be effective in reducing the massive inflammatory response seen in severe forms of COVID19.
Indeed, it did provide clinical benefit in a small group of patients by reducing their inflammatory parameters and improving their oxygenation.
The research was conducted by a team at the National Cancer Institute and elsewhere.
Acalabrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK).
BTK is part of the B-cell receptor (BCR) signaling pathway, which plays a central role in B-cell proliferation and survival, making it an important therapeutic target in the treatment of B-cell malignancies.
It is now approved in mantle cell lymphoma.
COVID19 disease is dividable into 3 clinical phases: the early phase (the viral phase where the SARS-COV-2 virus multiplies extensively), followed by the pulmonary phase (pneumonia with early hypoxia) and then the hyper inflammation phase, characterized by a cytokines storm, macrophages activation and accumulation of macrophages in the lungs, leading often to ICU admission and other complications with then much higher mortality.
The team says BTK inhibitors such as acalabrutinib may modulate this human inflammatory response particularly the innate immunity (i.e. “built-in” first defense type immunity by opposition to acquired immunity), dominated by macrophages reaction in response to the virus, but also reduce the cytokines storm through BTK-dependent suppression of NF-κB, a key factor in the production of multiple inflammatory cytokines and chemokines.
In the study, researchers gave acalabrutinib to 19 patients hospitalized with severe COVID-19 (11 receiving supplemental oxygen and 8 on ventilators).
After starting acalabrutinib, key measurements of inflammation such as CRP, IL6 and ferritin for example, improved in the majority of patients following a very similar pattern as shown in the paper, and which preceded oxygenation improvement of as well as of patients’ blood lymphocytes count.
Over a 10-14-day course of treatment, acalabrutinib improved blood oxygen levels in most patients, often within just one to three days, with no evidence of side effects.
After acalabrutinib treatment was completed eight of the eleven of the supplemental oxygen patients were discharged on “room” air and half of the mechanical ventilation patients had been extubated.
Overall patients did better if they were treated earlier in the course of their illness versus those who started acalabrutinib after they had been in the hospital for weeks on ventilator.
This was the case for the 1,000th patient discharged from Hackensack University Medical Center.
These results suggest that targeting excessive host inflammation with a BTK inhibitor might be a therapeutic strategy in severe COVID-19.
The study is published in Science Immunology.
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