Efficacy of Lefamulin for Community-Acquired Bacterial Pneumonia (CABP) Patients: Pooled Analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 1, LEAP 2 and LEAP China Trials.

Abstract

Purpose: Lefamulin represents a newly developed pleuromutilin antibiotic utilized for treating Community-Acquired Bacterial Pneumonia (CABP). Two pivotal Phase 3 studies, the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 trials, along with the bridging LEAP China trial, each confirmed that Lefamulin has proven efficacy and is non-inferior to active control treatments. This study conducted a post-hoc pooled analysis of these trials to assess Lefamulin's overall efficacy and its effects on specific patient groups, particularly the elderly and those at high risk of drug resistance.

Methods: Trials compared lefamulin to moxifloxacin in adults with CABP. The primary outcome was early clinical response (ECR). Secondary outcomes included investigator assessment of clinical response (IACR), and these responses in subgroups, such as severe patients, elderly patients, and those with prior antibiotic treatment. The pooled analysis was conducted post hoc, using noninferiority margin of 10% and 95% confidence intervals.

Results: Lefamulin (n=728) can provide sustained high efficacy, which was noninferior to moxifloxacin (n=683). ECR and IACR success rates demonstrated similar elevation (≥ 84.0%). Comparable and elevated ECR and IACR rates across subgroup of PORT risk class III to V(84.1-88.6%) and subgroup of prior antibiotic treatment (81.8-85.6%) were observed. In the subgroup of age over 65 years old, higher ECR of lefamulin vs moxifloxacin in each ten years-stratification (65-74 years old: 87.2% vs 86.5%; 75-84 years old: 86.8 vs 85.4%; ≥85 years old: 88.5 vs 82.4%). The older the age over 65 years old, the more favorable lefamulin.

Conclusion: Lefamulin, non-inferior to moxifloxacin, showed high effectiveness in CABP patients, especially in patients over 65 years old, those with PORT III-V or prior antibiotic treatment.