Nabriva Publishes Clinical Data Analysis Highlighting Benefits of Outpatient Management of Community Acquired Bacterial Pneumonia (CABP) with Oral XENLETA® (lefamulin)
-Post Hoc analysis published in
“In the treatment of CABP, initiating appropriate empiric oral antimicrobial therapy in the outpatient setting can result in significant economic benefits and successful infection control,” said Dr.
The LEAP 2 trial compared efficacy and safety of oral lefamulin 600 mg every 12 hours (5 days) versus oral moxifloxacin 400 mg every 24 hours (7 days) in adults (inpatients and outpatients) with Pneumonia Outcomes Research Team (PORT) risk classes II‒IV utilizing two outcome assessments of Early Clinical Response (ECR), an on-therapy endpoint, and Test of Cure (TOC), a post-therapy endpoint. In the post-hoc analysis, investigators examined data of 310 patients who started treatment as outpatients; 151 patients were treated with lefamulin and 159 were treated with moxifloxacin. Demographics and baseline clinical characteristics were generally similar between treatment groups and were broadly reflective of the patient population with CABP. In this cohort, 30% of outpatients were aged 65 years and older, and approximately 15% were aged 75 years and older. Among outpatients, the majority (lefamulin, 77%; moxifloxacin, 76%) entered the study with at least one comorbid condition or risk factor, such as age (65 or older), smoking history, history of hypertension, baseline liver enzyme elevation, moderate to severe renal impairment, history of asthma/COPD, diabetes mellitus, or history of arrhythmia), and 25% of patients in the lefamulin group and 29% in the moxifloxacin group had at least three comorbid conditions or risk factors.
Study findings showed that success rates at ECR/TOC for outpatients treated with oral lefamulin were high and similar to outpatients treated with moxifloxacin (lefamulin, 91% vs. moxifloxacin, 89%/90%), including those with PORT risk class III/IV (lefamulin, 89%/91% vs. moxifloxacin, 88%/91%) and CURB-65 scores of 2‒3 (lefamulin, 87%/90% vs. moxifloxacin, 82%/88%). In addition, the TOC success rate was maintained through late follow-up (Day 30±3 days) in both the lefamulin (91%) and moxifloxacin (90%) groups in outpatients.
Full results of the post-hoc analysis of LEAP 2 data is included in the paper titled: Oral 5-Day Lefamulin for Outpatient Management of Community-Acquired Bacterial Pneumonia: Post Hoc Analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 2 Trial, published in
LEAP 2 Study
The Phase 3, double-blind, double-dummy, parallel-group, noninferiority randomized trial was conducted in 99 sites in 19 countries. The clinical trial randomized 738 patients 18 years of age or older who had had PORT risk class II, III, or IV, radiographically documented pneumonia, acute illness, greater than three CABP symptoms, and greater than two vital sign abnormalities. Randomization was stratified by PORT risk class (II vs III/IV), geographic region (US vs ex-US), and prior receipt of a single dose of short-acting antibiotic therapy for CABP (yes vs no). Per protocol, ≤25 percent of the study population could have received a single dose of a short-acting antibiotic, and ≥50 percent were to have PORT risk class of III or IV. The first patient visit was on
Pneumonia is an infection of the lung that can be serious and fatal, especially among older adult patients with comorbidities. There are approximately five million cases of pneumonia in the
XENLETA® (lefamulin) is a first-in-class semi-synthetic pleuromutilin antibiotic for administration in humans discovered and developed by the
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INDICATION AND IMPORTANT SAFETY INFORMATION
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.
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
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.
Clostridium-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.
The most common adverse reactions (≥2%) 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
Please see Full Prescribing Information for XENLETA.
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1 Alexander E, Goldberg L, Das A. et al. Oral lefamulin vs moxifloxacin for early clinical response among adults with community-acquired bacterial pneumonia: the LEAP 2 randomized clinical trial. JAMA. 322(17):1661-1671.
Source: Nabriva Therapeutics US, Inc