New Crown Outbreak: 7.21 million cases worldwide! AstraZeneca BTK inhibitor Calquance: Improves clinical prognosis in most patients with severe COVID-19!

, June 09, 2020 /PRNewswire/ -- At present, the outbreak
of new crown pneumonia abroad is still spreading rapidlyAccording to Baidu's "New Coronavirus Pneumonia Epidemic Real-timeBig DataReport", as of 18:00 on June 09, 2020, the cumulative number of confirmed cases worldwide exceeded 7.217 million, and 7.132 million cases and 404,000 deaths were confirmed abroadAmong them, the United States confirmed a total of 2.026 million cases, 113,000 deathsthe unprecedented situation of the new crown epidemic, governments are urgently authorizing the potential for the treatment of severe neo-coronary pneumonia, including antiretroviral drugs, antimalarial drugs, anti-inflammatory drugs, plasma during rehabilitation, etcAt present, a number of pharmaceutical companies have been involved in the new coronavirus pneumonia (COVID-19) drug / vaccine research and development ranks,AstraZeneca, announced that the results of the study, published in the ScientificImmunology, show that the anti-cancer drug BTK inhibitor Calquence (acalabrutinib, acapinib) can reduce inflammatory markers and improve the clinical prognosis of patients with severe COVID-19The article is headlined:Inhibition of Bruton tyrosine kinase in patients with severe COVID-19
this article, a series of peer-reviewed cases of 19 hospitalized patients with COVID-19 disease and severe hypoxia and/or inflammation was conducted by U.S researchers, including AstraZeneca scientists, led by Dr Wyndham Wilson and Dr Louis Staud of the National Cancer Institute (NCI) of the National Institutes of Health." article describes the effects of calquance therapy on patients with severe respiratory diseases caused by the new coronavirus (SARS-CoV-2) Virally induced hyperimmune responses or "cytokine storms" are considered to be the main cause of respiratory disease in these patients, and there is evidence that the misalignment of BTK-dependent lung macrophage signaling mediates this cytokine storm and plays a role in COVID-19 pneumonia according to the article, 19 patients with severe COVID-19 (11 cases of oxygen supplementation, 8 cases of mechanical ventilation) were given Calquance off-label (off-label) medication, 18 of which had increased oxygen demand at baseline in a 10-14-day course, Calquence improved oxygenation in most patients, usually within 1-3 days, with no significant toxicity inflammatory indicators - C-reactive protein (CRP) and leukocyte interleukin 6 (IL-6) quickly returned to normal in most patients, and lymphocyte reduction quickly returned to normal and oxygenation improved accordingly At the end of Calquance treatment, 72.7 percent (8/11) of patients in the oxygen supplementary queue had stopped reoxygening and breathing indoor air; in vitro analysis showed that blood mononucleocells in patients with severe COVID-19 showed significantly increased BTK activity (self-phosphorylation) and increased IL-6 production compared to the blood mononucleoblasts of healthy volunteers these results show that targeting excessive host inflammation with BTK inhibitors is a treatment strategy for severe COVID-19 Based on this result, AstraZeneca has initiated a validated international prospective randomized controlled clinical trial "There is a strong scientific basis for supporting the investigation of the use of Calquence to treat patients with severe COVID-19," said Joss Baselga, executive vice president of cancer research and development at a of astrazenectoan The encouraging preliminary data presented in this case series provide information for the launch of the Global Phase II trial, in particular the CALAVI project We look forward to completing recruitment and obtaining data as soon as possible in these trials to learn more about what this potential treatment means for patients "
the BTK-dependent hypersensitivity immune response model in patients with COVID-19 (click on the image) the CALAVI project: in mid-April this year, AstraZeneca announced the launch of the CALAVI project to assess the potential for the over-immune response (cytokine storm) associated with THE treatment of COVID-19 infection in patients with severe patients The project includes two randomized, open-label, multicenter, global clinical trials
, one in the United States and one outside the United States (including Europe, Japan, South America) to assess Calquance's Joint Best Support Therapy (BSC), and the single BSC treatment of COVID-19 patients with respiratory complications, with the main therapeutic effect sized at the number of patients who survived and did not have respiratory failure COVID-19: this is a new pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Most cases of COVID-19 (about 80%) are mild respiratory diseases However, some patients require hospitalization, mainly due to pneumonia, and can rapidly develop into severe acute lung injury and acute respiratory distress syndrome (ARDS), which is associated with high mortality rates Virus-induced cytokine storms or "hyperimmune responses" are considered to be the main pathogenic mechanisms of ARDS in these patients by regulating lung macrophages, dendritic cells, and/or neutrophils Calquance: this is a new generation of selective BTK inhibitors, combined with BTK covalent, to inhibit its activity In B cells, the BTK signal causes the activation of multiple pathways necessary for B-cell proliferation, transport, chemization and adhesion In the United States and other countries, Calquance has been approved for the treatment of chronic lymphocytes leukemia (CLL) and cell lymphoma (MCL) in adults BTK inhibition: in lung macrophages, BTK is a key regulatory factor for the production of tally cell factors and chemofactors such as TNFa, IL-6, IL-10 and MCP-1 BTK inhibition reduces the production of these cytokines and is therefore a promising strategy for reducing COVID-19 respiratory complications evidence that the misaligned BTK-dependent macrophage signal may be at the heart of the SARS-COV-2 over-inflammatory response and play a role in COVID-19 pneumonia and ARDS TLR3, TLR7 and TLR8 in macrophages can identify single-stranded RNAs of viruses such as SARS-COV-2 and activate NF-kB and IRF3 signal conduction through BTK dependence, triggering the production of a variety of inflammatory cytokines and chemofactors In patients with of lymph node malignant tumors, therapeutic inhibition of BTK leads to reduction of pro-inflammatory cytokines and chemofactors, which supports the effect of BTK inhibition Similar findings were observed in the mouse influenza model, where BTK inhibition reduced these inflammatory media and saved mice from fatal acute lung injury (BioValleyBioon.com) original origin: Calquance showed ford clinical clinical sieops of 19 hospitalised COVID-19 patients