– All 6 patients treated with mavrilimumab showed resolution of fever and did not progress to mechanical ventilation; follow-on controlled study in Italy planned –
– Consortium of U.S. academic sites planning to commence investigator-initiated studies in parallel –
– Evaluating a Phase 2/3 clinical development program pending regulatory feedback and data from treatment experiences –
HAMILTON, Bermuda I March 31, 2020 IKiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (“Kiniksa”), a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients with significant unmet medical need, today announced early evidence of treatment response with mavrilimumab, an investigational fully-human monoclonal antibody that targets granulocyte macrophage colony stimulating factor receptor alpha (GM-CSFRα), 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.
“Patients with COVID-19 die of a devastating pneumonia caused by a hyperinflammation syndrome,” said Professor Lorenzo Dagna. “Last week my team administered mavrilimumab to 6 patients who were experiencing a steep decline of pulmonary status due to COVID-19 pneumonia. All patients responded on treatment, and 3 out of the 6 patients were discharged within 5 days. The data are compelling, and I look forward to continued studies of mavrilimumab in COVID-19.”
“These data are the first reported evidence of early treatment response with GM-CSF antagonism in COVID-19,” said John F. Paolini, MD, PhD, Chief Medical Officer of Kiniksa. “By blocking GM-CSF signaling, mavrilimumab works upstream of interleukin-6 and potentially addresses the underlying pathophysiology of the hyperinflammation which may be responsible for the severe pneumonia of COVID-19. Controlled clinical studies are required to fully characterize the potential of mavrilimumab in this disease. Building upon our activities over the last several weeks, we continue to evaluate the data and next steps, including a potential Phase 2/3 clinical development program.”
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,”1 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. 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 are thought to be drivers of a cytokine storm that plays a significant role in 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, results in 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 associated with mortality.
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 U.S. Food and Drug Administration (FDA) regarding the path forward for potential Phase 2/3 clinical development of mavrilimumab in COVID-19 pneumonia.
Mavrilimumab is an investigational agent and is not approved for any indication in any country.
1 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.
About Kiniksa
Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa’s clinical-stage product candidates, rilonacept, mavrilimumab, KPL-716 and KPL-404, are based on strong biologic rationale or validated mechanisms, target underserved conditions and offer the potential for differentiation. These pipeline assets are designed to modulate immunological signaling pathways that are implicated across a spectrum of diseases. For more information, please visit www.kiniksa.com.
About Mavrilimumab
Mavrilimumab is an investigational fully-human monoclonal antibody that is designed to antagonize GM-CSF signaling by binding to the alpha subunit of the GM-CSF receptor (GM-CSFRα). Kiniksa’s lead indication for mavrilimumab is giant cell arteritis (GCA), an inflammatory disease of medium-to-large arteries. Mavrilimumab was dosed in over 550 patients with rheumatoid arthritis through Phase 2b clinical studies in Europe and achieved prospectively-defined primary endpoints of efficacy and safety. Additionally, Kiniksa and Kite, a Gilead company, have a clinical collaboration to evaluate mavrilimumab in combination with Yescarta® (axicabtagene ciloleucel) in patients with relapsed or refractory large B-cell lymphoma.
SOURCE: Kiniksa
Post Views: 274
– All 6 patients treated with mavrilimumab showed resolution of fever and did not progress to mechanical ventilation; follow-on controlled study in Italy planned –
– Consortium of U.S. academic sites planning to commence investigator-initiated studies in parallel –
– Evaluating a Phase 2/3 clinical development program pending regulatory feedback and data from treatment experiences –
HAMILTON, Bermuda I March 31, 2020 IKiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (“Kiniksa”), a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients with significant unmet medical need, today announced early evidence of treatment response with mavrilimumab, an investigational fully-human monoclonal antibody that targets granulocyte macrophage colony stimulating factor receptor alpha (GM-CSFRα), 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.
“Patients with COVID-19 die of a devastating pneumonia caused by a hyperinflammation syndrome,” said Professor Lorenzo Dagna. “Last week my team administered mavrilimumab to 6 patients who were experiencing a steep decline of pulmonary status due to COVID-19 pneumonia. All patients responded on treatment, and 3 out of the 6 patients were discharged within 5 days. The data are compelling, and I look forward to continued studies of mavrilimumab in COVID-19.”
“These data are the first reported evidence of early treatment response with GM-CSF antagonism in COVID-19,” said John F. Paolini, MD, PhD, Chief Medical Officer of Kiniksa. “By blocking GM-CSF signaling, mavrilimumab works upstream of interleukin-6 and potentially addresses the underlying pathophysiology of the hyperinflammation which may be responsible for the severe pneumonia of COVID-19. Controlled clinical studies are required to fully characterize the potential of mavrilimumab in this disease. Building upon our activities over the last several weeks, we continue to evaluate the data and next steps, including a potential Phase 2/3 clinical development program.”
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,”1 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. 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 are thought to be drivers of a cytokine storm that plays a significant role in 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, results in 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 associated with mortality.
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 U.S. Food and Drug Administration (FDA) regarding the path forward for potential Phase 2/3 clinical development of mavrilimumab in COVID-19 pneumonia.
Mavrilimumab is an investigational agent and is not approved for any indication in any country.
1 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.
About Kiniksa
Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa’s clinical-stage product candidates, rilonacept, mavrilimumab, KPL-716 and KPL-404, are based on strong biologic rationale or validated mechanisms, target underserved conditions and offer the potential for differentiation. These pipeline assets are designed to modulate immunological signaling pathways that are implicated across a spectrum of diseases. For more information, please visit www.kiniksa.com.
About Mavrilimumab
Mavrilimumab is an investigational fully-human monoclonal antibody that is designed to antagonize GM-CSF signaling by binding to the alpha subunit of the GM-CSF receptor (GM-CSFRα). Kiniksa’s lead indication for mavrilimumab is giant cell arteritis (GCA), an inflammatory disease of medium-to-large arteries. Mavrilimumab was dosed in over 550 patients with rheumatoid arthritis through Phase 2b clinical studies in Europe and achieved prospectively-defined primary endpoints of efficacy and safety. Additionally, Kiniksa and Kite, a Gilead company, have a clinical collaboration to evaluate mavrilimumab in combination with Yescarta® (axicabtagene ciloleucel) in patients with relapsed or refractory large B-cell lymphoma.
SOURCE: Kiniksa
Post Views: 274
