Kiniksa Pharmaceuticals Ltd (NASDAQ: KNSA) stock rose 27.17% on March 31st, 2020 (Source: Finviz.com) and continued its recovery, rising over 5.6% on 1st April, 2020 (as of 10:48 am GMT-4; Source: Google finance). The company announced that mavrilimumab, which is an investigational, fully-human monoclonal antibody that targets granulocyte macrophage colony stimulating factor receptor alpha (GM-CSFRa), in a treatment protocol, has showed positive response in patients with severe COVID-19 pneumonia and hyper inflammation. The patients suffering from severe pulmonary involvement of COVID-19, acute respiratory distress, fever, and clinical and biological markers of systemic hyperinflammation status were treated with a single intravenous dose of mavrilimumab. The objective is the reduction of incidence of progression of acute respiratory failure, the need of mechanical ventilation, and the transfer to the intensive care unit.
To date, the company has treated 6 patients with mavrilimumab in the treatment protocol. All patients showed an early resolution of fever and improvement in oxygenation within 1-3 days. None of these patients then required mechanical ventilation. All patients has responded on treatment, and 3 out of the 6 patients were discharged within 5 days.
These data are the first reported evidence of early treatment response with GM-CSF antagonism in COVID-19. By blocking GM-CSF signaling, mavrilimumab works upstream of interleukin-6 and then addresses the underlying pathophysiology of the hyperinflammation that may be responsible for the severe pneumonia of COVID-19. Controlled clinical studies are needed to fully characterize the potential of mavrilimumab in this disease. Based upon the activities over the last several weeks, the company is evaluating the data and next steps, that includes a potential Phase 2/3 clinical development program after getting the regulatory (Food and Drug Administration) feedback. Kiniksa and its collaborators are planning to commence investigator-initiated studies in parallel.
Meanwhile, Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocyte in severe pulmonary syndrome patients of a new coronavirus, that offers scientific rationale regarding granulocyte macrophage colony stimulating factor (GM-CSF) in the mechanism of excessive and aberrant immune cell infiltration and activation in the lungs which contribute to mortality in the disease. The emerging data indicate that patients with COVID-19 have elevated serum levels of pro-inflammatory cytokines, including GM-CSF, and interferon-gamma (IFN-γ), which boost cytokine storm that leads to clinical complications and acute lung injury. Infiltration of immune cells in the lungs of COVID-19 patients, as part of an exaggerated immune response despite falling viral loads, lead to severe lung complications. These data suggest that it may be the excessive, non-effective host immune response by pathogenic T cells and inflammatory monocytes that causes the severe lung pathology most often related with mortality.