717. Lefamulin (LEF) vs. Moxifloxacin (MOX) in Patients With Community-Acquired Bacterial Pneumonia (CABP) at Risk for Poor Efficacy or Safety Outcomes: Pooled Subgroup Analyses From the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 Noninferiority Clinical Trials

Abstract

BackgroundIn the United States, CABP is the second most common cause of hospitalization and a leading cause of infectious death. Patients with chronic obstructive pulmonary disease (COPD)/asthma or diabetes are at risk for CABP and associated mortality. Similarly, patients with underlying cardiac or liver disease are at risk for potential cardiac or liver toxicities, respectively, associated with CABP antimicrobials, and patients aged ≥65 years are at risk for both efficacy/safety concerns. We report pooled efficacy/safety outcomes in at-risk subgroups from the LEAP 1 and 2 phase 3 trials.MethodsIn LEAP 1, patients with CABP (PORT III–V) received IV LEF 150 mg q12h for 5–7 days or MOX 400mg q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, patients with CABP (PORT II–IV) received oral LEF 600 mg q12h for 5 days or MOX 400 mg q24h for 7 days. Both studies assessed early clinical response (ECR; 96 ± 24 hours after first dose) in the intent-to-treat (ITT; all randomized patients) population (FDA primary endpoint) and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (≥1 study drug dose) and clinically evaluable (met predefined evaluability criteria) populations (EMA coprimary endpoints). Pooled analyses used a 10% noninferiority margin. Safety was assessed in all randomized and treated patients.Results1289 ITT patients were randomized to LEF (n = 646) or MOX (n = 643); of whom, 297 (23.0%) were aged 65–74 years and 220 (17.1%) were ≥75 years; 232 patients (18.0%) had COPD/asthma and 168 (13.0%) had diabetes mellitus (DM). At baseline, 501 patients (38.9%) had history of hypertension, 73 (5.7%) had history of arrhythmia, and 263 (20.4%) had transaminitis. The figure shows efficacy by age and in COPD/asthma and DM patients. Treatment-emergent adverse events, electrocardiogram assessments, and laboratory results in patients at risk for cardiac and hepatic safety concerns are shown in Tables 1 and 2.ConclusionIn pooled analyses of LEAP 1 and 2, LEF efficacy was high and similar to MOX in patients at risk of efficacy concerns and LEF showed a safety profile similar to that of MOX in patients at risk of safety concerns. LEF is a promising new option for IV/oral monotherapy of CABP in patients at risk of poor outcomes due to CABP or to antimicrobial therapy for CABP. Disclosures All authors: No reported disclosures.