DUBLIN, Ireland, Sept. 27, 2019 (GLOBE NEWSWIRE) -- Nabriva Therapeutics plc (NASDAQ: NBRV), a biopharmaceutical company engaged in the commercialization and development of innovative anti-infective agents to treat serious infections, announced today that the Journal of the American Medical Association (JAMA) has published results from the company’s Lefamulin Evaluation Against Pneumonia 2 (LEAP 2) clinical trial. The U.S. Food and Drug Administration (FDA) approved lefamulin on August 19, 2019 under the brand name XENLETA™, which is now available for the treatment of adults with CABP. XENLETA is the first IV and oral antibiotic with a novel mechanism of action approved by the FDA in nearly two decades.
In the study, the second of two global, pivotal Phase 3 clinical trials of lefamulin, clinicians evaluated the safety and efficacy of five days of oral lefamulin compared to seven days of oral moxifloxacin, a respiratory fluoroquinolone, in adult patients with moderate CABP (PORT risk class II, III, or IV). In this study, a short course (5-days) of lefamulin was shown to be noninferior to a 7-day regimen of moxifloxacin for the treatment of CABP. Lefamulin achieved high clinical response rates for both typical (Streptococcus pneumoniae - including multi-drug resistant strains, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus), as well as atypical pathogens (Mycoplasma pneumoniae, including macrolide-resistant strains, Chlamydophila pneumoniae, and Legionella pneumophila). Both lefamulin and moxifloxacin were generally well tolerated with low and similar incidence of discontinuations due to adverse events.
“The increasing prevalence of antimicrobial resistance in the most common causative pathogens of CABP, along with growing evidence of safety concerns with fluoroquinolones makes a compelling case for the development of new antibacterial classes with novel mechanisms of action (MOA) to treat patients with CABP,” said Jennifer Schranz, MD, Chief Medical Officer of Nabriva Therapeutics. “Xenleta is the first novel MOA antibiotic approved in the United States in nearly 20 years. The results from the LEAP clinical trial program, combined with lefamulin’s targeted spectrum of activity, which aligns with the principles of antimicrobial stewardship, make it an attractive short-course, monotherapy treatment option for adults with CABP.”
The publication, entitled “Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults with Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial,” is available online.
In a related editorial published in the same edition, entitled “Lefamulin – A New antibiotic for Community-Acquired Pneumonia,” author Preeti N. Malani, MD, MSJ, Division of Infectious Diseases at the University of Michigan and Associate Editor of JAMA, states “…lefamulin is an important addition to the current antibiotic armamentarium, especially because bacterial pneumonia remains one of the most common indications for antibiotic use.”
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 Pneumonia Outcomes Research Team (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 August 30, 2016, and patients were followed for 30 days, with the final date of follow-up on January 2, 2018.
Patients were randomized 1:1 to receive oral lefamulin (600 mg every 12 hours for 5 days; n = 370) or moxifloxacin (400 mg every 24 hours for 7 days; n = 368).
The primary endpoint for the study was early clinical response (ECR) at 96±24 hours after the first dose of either study drug in the intent-to-treat (ITT) population (all randomized patients). Responders were defined as alive, showing improvement in greater than two or more of the four CABP symptoms, having no worsening of any CABP symptoms, and not receiving any non-study antibacterial drug for current CABP episode. The European Medicines Agency coprimary endpoints (FDA secondary endpoints) were investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (mITT; randomized and received any amount of study drug) population and in the clinically evaluable (CE; met pre-defined inclusion/exclusion criteria, minimal dosing requirements) population. The noninferiority margin was 10 percent for ECR and IACR.
Study results showed that ECR rates were 90.8 percent with lefamulin and 90.8 percent with moxifloxacin, meeting the noninferiority margin of 10 percent. IACR rates were 87.5 percent with lefamulin and 89.1 percent with moxifloxacin in the modified ITT population and 89.7 percent and 93.6 percent, respectively, in the clinically evaluable population at test of cure. Lefamulin was well tolerated during the trial. The most frequently reported treatment-emergent adverse events for lefamulin were diarrhea, nausea and vomiting, predominantly mild to moderate, manageable and which rarely led to discontinuation.
“The results from this randomized clinical trial will inform more clinicians of lefamulin’s potential as an effective alternative to commonly used antibiotics, such as fluoroquinolones or macrolides, to fight community acquired pneumonia, which affects five million Americans each year,” said Gregory Moran, MD., Chief, Olive View-UCLA Medical Center.
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 indicated for the treatment of adults with CABP caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. It is designed to inhibit the synthesis of bacterial protein, which is required for bacteria to grow. XENLETA’s binding occurs with high affinity and high specificity at molecular sites that are different than other antibiotic classes, resulting in a lower risk of developing resistance and cross-resistance to other commonly used ...
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