The latest contestant in the race for drugs to treat Covid-19 has entered the clinic, this time a medicine used to treat blood cancers, its manufacturer said.
London-based AstraZeneca said Tuesday that it had initiated a clinical trial, titled CALAVI, investigating the drug Calquence (acalabrutinib) in treating cytokine storm – a kind of overactive immune system response – in Covid-19 patients and that the study would start enrolling patients in the coming days.
The company’s announcement did not specify the phase of the trial, which is apparently not yet listed on ClinicalTrials.gov or the European Union Clinical Trials Register. However, it described CALAVI as a large, multicenter and global trial randomizing patients to receive Calquence on top of standard treatment or standard treatment alone and said it would start opening sites in the U.S. and some European countries. The trial’s design consists of two parts, one in patients who are hospitalized but not on ventilation, and another in patients with more severe respiratory complications. The study will measure rates of ventilation use and death.
Calquence is a BTK inhibitor approved for treating mantle cell lymphoma and chronic lymphocytic leukemia. In Covid-19, it is being investigated not as an antiviral, but rather to see if it can mitigate cytokine storm, which is a leading cause of mortality and death in severely ill patients. Because of the role of BTK – which stands for Bruton’s tyrosine kinase – in the production of inflammatory cytokines and chemokines like TNF-alpha, IL-6, IL-10 and MCP-1, the company explained, inhibiting the kinase represents a potential strategy for reducing respiratory complications of Covid-19. The company cited evidence that dysregulated signaling by immune cells known as macrophages that is dependent on BTK may be central to the cytokine storms that Covid-19 patients experience.
Other BTK inhibitors include AbbVie and Johnson & Johnson’s Imbruvica (ibrutinib) and BeiGene’s Brukinsa (zanubrutinib). A search on ClinicalTrials.gov and the E.U. registry did not find turn up trials for either drug in Covid-19, and neither drug’s manufacturers have issued press statements announcing trials.
Several other drugs are also being tested as potential therapies for cytokine storm and inflammation related to Covid-19. These include monoclonal antibodies used for autoimmune diseases like Roche’s Actemra (tocilizumab) and Regeneron Pharmaceuticals and Sanofi’s Kevzara (sarilumab). Several JAK inhibitors – used to treat rheumatoid arthritis as well as in some cases certain blood cancers – are also in development, including Incyte and Novartis’ Jakafi (ruxolitinib), Pfizer’s Xeljanz (tofacitinib) and Eli Lilly’s Olumiant (baricitinib).