Nabriva (NBRV) Publishes Data Demonstrating the Potent Anti-Inflammatory Properties of XENLETA
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Nabriva Therapeutics plc (NASDAQ: NBRV), a biopharmaceutical company engaged in the commercialization and development of innovative anti-infective agents to treat serious infections, today published the first data to demonstrate the anti-inflammatory activity of XENLETA® (lefamulin).
The nonclinical study, entitled “Anti-inflammatory activity of lefamulin versus azithromycin and dexamethasone in vivo and in vitro in a lipopolysaccharide-induced lung neutrophilia mouse model,” was published in the peer-reviewed journal, PLOS ONE.
XENLETA is the first intravenous and oral pleuromutilin approved for the systemic treatment of community acquired bacterial pneumonia (CABP) in adults. In this nonclinical study of inflammatory lung disease, XENLETA potently inhibited inflammation caused by the migration of neutrophils (a type of white blood cell) in the lungs of mice. Importantly, XENLETA also reduced pro-inflammatory cytokines comparable to that observed with dexamethasone (a potent corticosteroid) and greater than that of azithromycin, a macrolide antibiotic commonly utilized for its anti-inflammatory properties.
“Infection in the lung is associated with an acute inflammatory reaction that can complicate a patient’s clinical course and make treatment more difficult,” said Steve Gelone, Pharm.D., Nabriva’s President and Chief Operating Officer, and a co-author of the study. “We believe an agent that combines potent antibacterial and anti-inflammatory properties may offer clinicians a differentiated treatment option for their patients. We look forward to continuing to evaluate XENLETA’s ability to mitigate the inflammatory response and exploring its clinical applications.”
“These findings are important as they suggest lefamulin has anti-inflammatory properties, along with its proven anti-infective activity,” said Dr. Thomas File, Jr. MD, MSc, MACP, FIDSA, FCCP and Chair of the Infectious Disease Division at Summa Health. “The potential to address two serious problems – the bacterial infection and concurrent inflammation – with a single agent may offer patients with acute lung disorders a more convenient treatment option.”
In this study, the anti-inflammatory effects of XENLETA were evaluated in a mouse model of lung inflammation induced by a toxin called lipopolysaccharide that simulates acute respiratory distress syndrome (ARDS) similar to that seen with SARS-CoV-2 infection. Single subcutaneous doses of lefamulin (10‒140mg/kg) resulted in reductions of several measurements of inflammation: dose-dependent reductions of bronchoalveolar lavage fluid neutrophil cell counts, pro-inflammatory cytokine (TNF-α, IL-6, IL-29 1β, and GM-CSF), chemokine (CXCL-1, CXCL-2, and CCL-2), and MMP-9 levels that were comparable to or more potent than single oral/intraperitoneal dexamethasone (0.5/1mg/kg) or subcutaneous azithromycin (10‒100mg/kg).
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