According to the researchers, the cancer drug acalabrutinib blocked the protein Bruton tyrosine kinase (BTK) in COVID-19 patients, and provided clinical benefit to a small group of them.
Scientists have observed that a drug which is already approved to treat several blood cancers, is associated with reduced respiratory distress and a reduction in the overactive immune response in COVID-19 patients, an advance that may lead to a potential therapeutic for novel coronavirus infection. According to the researchers, including those from the National Cancer Institute in the US, the cancer drug acalabrutinib blocked the protein Bruton tyrosine kinase (BTK) in COVID-19 patients, and provided clinical benefit to a small group of them.
The study, published in the journal Science Immunology, noted that the findings should not be considered clinical advice, and remain to be tested in a randomised, controlled clinical trial. The BTK protein, according to the scientists, plays an important role in the immune system, including in macrophages which are immune cells that can cause inflammation by producing proteins known as cytokines. These proteins, the researchers said, act as chemical messengers that help to stimulate and direct the immune response.
In some patients with severe COVID-19, the study said a large amount of cytokines are released in the body all at once, causing the immune system to damage the function of organs such as the lungs — a process known as a “cytokine storm.” The current study involved 19 patients with a confirmed COVID-19 diagnosis that required hospitalisation, as well as with low blood-oxygen levels and evidence of inflammation. According to the scientists, 11 of the 19 patients had been receiving supplemental oxygen for a median of two days, and eight others had been on ventilators for a median of 1.5 days.
The study noted that within one to three days after they began receiving the cancer drug, majority of patients in the supplemental oxygen group experienced a substantial drop in inflammation, and their breathing improved. It said eight of the 11 patients were able to come off supplemental oxygen, and were discharged from the hospital.
Although the benefit of acalabrutinib was reported to be less dramatic in patients on ventilators, the scientists said four of the eight patients were able to come off the ventilator, two of whom were eventually discharged. According to the scientists, the ventilator patient group was extremely clinically diverse and included patients who had been on a ventilator for prolonged periods of time and had major organ dysfunction. Two of the patients in this group died, they said.
An analysis of blood samples from the patients revealed that the levels of interleukin-6 (IL-6), a major cytokine associated with hyperinflammation in severe COVID-19, decreased after treatment with acalabrutinib. The scientists said counts of lymphocytes, an immune cell type associated with worse outcome in COVID-19 patients, also rapidly improved in most patients.
When the researchers tested blood cells from patients with severe COVID-19, who were not in the study, and compared it with samples from healthy volunteers, they found that the patients with severe COVID-19 had higher activity of the BTK protein and greater production of IL-6. Based on these findings, they suggested that acalabrutinib may have been effective since its target, BTK, is hyperactive in severe COVID-19 immune cells.
However, in a note of caution, the scientists also mentioned in the study that the most common adverse events associated with long-term acalabrutinib therapy included “low-grade headache, diarrhea, pyrexia and upper respiratory tract infections.” They said the safety profile of acalabrutinib in patients with severe COVID-19 needs to be confirmed in a prospective clinical trial. “Further correlative studies will be needed to understand the basis for response or resistance to BTK inhibition in patients with such advanced disease,” the scientists wrote in the study.