---- Nabriva Publishes Data Demonstrating the Potent Anti-Inflammatory Properties of XENLETA(R) (lefamulin)
2021-10-04 05:09:01 PM ET (GlobeNewswire)
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 (10â?'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 1B, 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 (10â?'100mg/kg).
About XENLETA
XENLETA (lefamulin) is a first-in-class semi-synthetic pleuromutilin antibiotic for systemic administration in humans discovered and developed by the Nabriva Therapeutics team. It is designed to inhibit the synthesis of bacterial protein, which is required for bacteria to grow. XENLETA's binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes. Efficacy of XENLETA was demonstrated in two multicenter, multinational, double-blind, double-dummy, non-inferiority trials assessing a total of 1,289 patients with CABP. In these trials, XENLETA was compared with moxifloxacin and in one trial, moxifloxacin with and without linezolid. Patients who received XENLETA had similar rates of efficacy as those taking moxifloxacin alone or moxifloxacin plus linezolid. The most common adverse reactions associated with XENLETA included diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. For more information, please visit www.XENLETA.com.
Indication and Important Safety Information
Indication
XENLETA is a pleuromutilin antibacterial indicated for the treatment of adults with community-acquired bacterial pneumonia (CABP) caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of XENLETA and other antibacterial drugs, XENLETA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
Important Safety Information
CONTRAINDICATIONS
XENLETA is contraindicated in patients with known hypersensitivity to XENLETA or pleuromutilins.
XENLETA tablets are contraindicated for use with CYP3A4 substrates that prolong the QT interval.
WARNINGS AND PRECAUTIONS
XENLETA has the potential to prolong the QT interval. Avoid XENLETA in patients with known QT prolongation, ventricular arrhythmias, and patients receiving drugs that may prolong the QT interval.
Based on animal studies, XENLETA may cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.
Clostridioides difficile-associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including XENLETA, with severity ranging from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs.
ADVERSE REACTIONS
The most common adverse reactions (greater-than or equal to2%) for (a) XENLETA Injection are administration site reactions, hepatic enzyme elevation, nausea, hypokalemia, insomnia, and headache and (b) XENLETA Tablets are diarrhea, nausea, vomiting, and hepatic enzyme elevation.
USE IN SPECIFIC POPULATIONS
In patients with severe hepatic impairment, reduce the dosage of XENLETA Injection to 150 mg infused over 60 minutes every 24 hours. XENLETA Tablets are not recommended in patients with moderate or severe hepatic impairment due to insufficient information to provide dosing recommendations.
Avoid XENLETA Injection and Tablets with concomitant strong or moderate CYP3A or P-gp inducers. Monitor for reduced efficacy of XENLETA.
Avoid XENLETA Tablets with strong CYP3A or P-gp inhibitors.
Monitor for adverse reactions of sensitive CYP3A substrates administered with XENLETA Tablets.
XENLETA has not been studied in pregnant women. Verify pregnancy status in females prior to initiating XENLETA and advise females to use contraception during treatment and for 2 days after the final dose. Lactating women should pump and discard milk for the duration of treatment with XENLETA and for 2 days after the final dose.
To report SUSPECTED ADVERSE REACTIONS, or administration during pregnancy, contact Nabriva Therapeutics US, Inc. at 1-855-5NABRIVA or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see Full Prescribing Information for XENLETA.
About Nabriva Therapeutics plc
Nabriva Therapeutics is a biopharmaceutical company engaged in the commercialization and development of innovative anti-infective agents to treat serious infections. Nabriva Therapeutics received U.S. Food and Drug Administration approval for XENLETA(R) (lefamulin injection, lefamulin tablets), the first systemic pleuromutilin antibiotic for community-acquired bacterial pneumonia (CABP). Nabriva Therapeutics is also developing CONTEPO(TM) (fosfomycin) for injection, a potential first-in-class epoxide antibiotic for complicated urinary tract infections (cUTI), including acute pyelonephritis. Nabriva entered into an exclusive agreement with subsidiaries of Merck & Co. Inc., Kenilworth, N.J., USA to market, sell and distribute SIVEXTRO(R) (tedizolid phosphate) in the United States and certain of its territories.
