Kiniksa Pharmaceuticals, Ltd. announced early evidence of treatment response with mavrilimumab, an investigational fully-human monoclonal antibody that targets granulocyte macrophage colony stimulating factor receptor alpha (GM-CSFR alpha), in a treatment protocol in patients with severe coronavirus 2019 (COVID-19) pneumonia and hyperinflammation.
The treatment protocol was conducted by Professor Lorenzo Dagna, MD, FACP, Head, Unit of Immunology, Rheumatology, Allergy and Rare Diseases IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University in Milan, Italy within a COVID-19 Program directed by Professor Alberto Zangrillo, Head of Department of Anesthesia and Intensive Care of the Scientific Institute San Raffaele Hospital and Professor in Anesthesiology and Intensive Care, Università Vita-Salute San Raffaele.
The treatment protocol with the investigational drug mavrilimumab was a prospective, interventional, single-active-arm, single-center pilot experience. 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 was to reduce incidence of progression of acute respiratory failure, the need of mechanical ventilation, and the transfer to the intensive care unit.
To date, 6 patients have been treated 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 have progressed to require mechanical ventilation. Mavrilimumab has been well-tolerated.
Kiniksa and its collaborators are planning the following in the near-term: Professor Dagna plans to initiate a prospective, single-center investigator-initiated study based on the initial results from the treatment protocol. The primary objective will be prevention of respiratory failure. A consortium of U.S. academic sites plans to initiate parallel prospective, interventional studies with mavrilimumab in patients with severe COVID-19 pneumonia and hyperinflammation. Kiniksa is engaging with the FDA regarding the path forward for potential Phase II/III clinical development of mavrilimumab in COVID-19 pneumonia.
Recent data published in a paper titled, “Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocyte in severe pulmonary syndrome patients of a new coronavirus,” provide scientific rationale implicating granulocyte macrophage colony stimulating factor (GM-CSF) in the mechanism of excessive and aberrant immune cell infiltration and activation in the lungs thought to contribute significantly to mortality in the disease.
See- Zhou Y, Fu B, Zheng X, et al. "Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus". Pre-Print. 2020 .