664. Efficacy in Adults With Moderate to Severe Community-Acquired Bacterial Pneumonia (CABP) and Pneumonia Outcomes Research Team (PORT) Risk Class III to V: Results of a Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Outcomes

Abstract Background CABP, the second most common cause of hospitalization in the US, has prognoses ranging from rapid resolution to death, the likelihood of which can be estimated via PORT pneumonia severity index. Patients with PORT scores ≤III have predicted mortality rates <3% and may be managed as outpatients; those with scores of IV/V are often hospitalized, owing to higher predicted mortality rates (8%–31%). Lefamulin (LEF), a novel systemic antibiotic, was noninferior to moxifloxacin (MOX) for treatment of adults with CABP in 2 phase 3 trials (LEAP 1 and 2). We report the results of pooled analyses of LEAP 1/2 data in patients with PORT III and IV/V scores. Methods In LEAP 1, patients (PORT III–V) received IV LEF 150 mg for 5–7 d or MOX 400 mg for 7 d, with optional IV-to-oral switch. In LEAP 2, patients (PORT II–IV) received oral LEF 600 mg for 5 d or MOX 400 mg for 7 d. In both studies, randomization was stratified by PORT score. The studies assessed early clinical response (ECR; 96±24 h after first dose) in the intent-to-treat (ITT; all randomized patients) population (FDA primary endpoint) and investigator assessment of clinical response (IACR) success at test of cure (5–10 d after last dose) in the modified ITT (received ≥1 dose) and clinically evaluable (met predefined evaluability criteria) populations (EMA coprimary endpoints). Results Over 50% of patients (52.8% LEF; 51.9% MOX) were PORT III and >18% (18.7% LEF; 18.2% MOX) were PORT IV/V, reflective of the CABP population. As expected, PORT IV/V patients were older and more likely to have comorbidities (eg, moderate/severe renal impairment) vs. PORT III patients (Table 1). ECR and IACR response rates were high and similar for LEF and MOX in PORT III (Figure 1) and PORT IV/V (Figure 2) patients, with slightly higher rates in PORT III vs. PORT IV/V patients. LEF and MOX had similar safety profiles, with more adverse events overall in PORT IV/V vs. PORT III patients (Table 2). Mortality rates were low, with higher rates in PORT IV/V (4.2% LEF; 5.2% MOX) vs. PORT III (1.5% LEF; 0.6% MOX) patients. Conclusion ECR and IACR rates with LEF were high and similar to MOX in patients who are candidates for outpatient (PORT III) and inpatient (PORT IV/V) treatment; LEF may be an alternative oral and IV monotherapy option for empiric CABP treatment in both populations. Disclosures All authors: No reported disclosures.