- All 6 patients treated with mavrilimumab showed resolution of fever and did not progress to mechanical ventilation; follow-on controlled study in
- Evaluating a Phase 2/3 clinical development program pending regulatory feedback and data from treatment experiences -
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
“These data are the first reported evidence of early treatment response with GM-CSF antagonism in COVID-19,” said
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 Dagnaplans 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.
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.
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
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential,” “evaluate” or “continue” or the negative of these terms or other similar expressions, although not all forward‑looking statements contain these identifying words. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding: the anticipated prospective, interventional, single-active-arm study of mavrilimumab in patients with severe COVID-19; plans by a
These forward-looking statements are based on management’s current plans, estimates or expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including without limitation, the following: potential delays or difficulty in enrollment of patients in, and activation or continuation of sites for, investigator-initiated investigational treatment or studies with mavrilimumab in patients with severe COVID-19 pneumonia and hyperinflammation; potential complications in coordinating among requirements, regulations and guidelines of regulatory authorities across a number of jurisdictions for such investigational treatment or studies; potential undesirable side effects caused by mavrilimumab in patients with severe COVID-19 pneumonia and hyperinflammation or otherwise; our potential inability to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities or otherwise producing negative, inconclusive or commercially uncompetitive results; potential for changes between initial data interpretations and later, additional or other data generated from the investigational treatment or studies we announce; impact of additional data from us or other companies; our potential inability to replicate in clinical trials positive results from the investigational treatment or studies with mavrilimumab in patients with severe COVID-19 pneumonia and hyperinflammation; drug substance and/or drug product shortages of mavrilimumab; our reliance on third parties as the sole source of supply of the drug substance and drug products used in our product candidates, including mavrilimumab; our reliance on third parties to conduct investigator-initiated investigational treatment or studies with mavrilimumab in patients with severe COVID-19 pneumonia and hyperinflammation; changes in our operating plan and funding requirements; substantial existing or new competition; and our ability to attract and retain qualified personnel.
These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K filed with the
Yescarta® is a registered trademark of Gilead Sciences, Inc., or its related companies.
Every Second Counts!™
Kiniksa Investor and Media Contact
Source: Kiniksa Pharmaceuticals, Ltd.