LEFAMULIN EFFICACY AND SAFETY IN ADULTS WITH COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA: POOLED ANALYSIS OF THE LEFAMULIN EVALUATION AGAINST PNEUMONIA (LEAP) 1 AND LEAP 2 TRIALS BY AGE, INCLUDING IN PATIENTS AGED ≥85 YEARS

Abstract

SESSION TITLE: Chest Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Community-acquired bacterial pneumonia (CABP) is the most common cause of infectious death in US adults aged >65y. Worldwide, the aging population is increasing, and older patients (pts) with CABP are especially at risk, with higher hospitalization and mortality rates than younger pts. Those with advanced age are more vulnerable to having or developing CABP complications, and treatment is often more difficult in these pts (eg, due to multimorbidity, immunosenescence, polypharmacy). The efficacy/safety of lefamulin (LEF), a novel pleuromutilin approved for intravenous (IV) and oral use in adults with CABP, were shown in 2 noninferiority phase 3 trials, LEAP 1 and LEAP 2. Here, we report pooled LEAP 1 and 2 efficacy/safety outcomes by age group (18-64, 65-74, 75-84, and ≥85y). METHODS: In LEAP 1, adults with CABP (PORT risk class III–V) received IV LEF 150mg q12h for 5–7d or moxifloxacin (MOX) 400mg q24h for 7d, with optional IV-to-oral switch (LEF 600mg q12h or MOX 400mg q24h). In LEAP 2, adults with CABP (PORT II–IV) received oral LEF 600mg q12h (5d) or MOX 400mg q24h (7d). Both studies assessed early clinical response (ECR) at 96±24h after first study drug dose in the intent-to-treat (ITT) population (all randomized pts) and investigator assessment of clinical response (IACR) at test of cure (TOC; 5–10d after last dose) in the modified ITT (received ≥1 study drug dose) and clinically evaluable (met predefined evaluability criteria) populations. Treatment-emergent adverse events (TEAEs) were also assessed. RESULTS: In the pooled ITT population, 1289 pts were randomized to LEF (n=646) or MOX (n=643); 772 (59.9%) were aged 18–64y, 297 (23.0%) were 65–74y, 177 (13.7%) were 75–84y, and 43 (3.3%) were ≥85y. Older pts (ages 75–84y, ≥85y) were more likely to have comorbidities (eg, moderate/severe renal impairment, hypertension, arrhythmia) vs younger pts (ages 18–64y, 65–74y). For all age groups, high and similar ECR (LEF ≥88%; MOX ≥82%) and IACR success (LEF ≥82%; MOX ≥83%) rates were seen with each treatment, including in pts aged ≥85y (ECR: 88.5% [LEF] vs 82.4% [MOX]; IACR success: 88.5%-95.5% vs 88.2%-100%). The most common TEAEs were gastrointestinal, with generally similar rates across age groups for LEF (8.6%–15.0%) and MOX (5.9%–14.0%). With both treatments, rates of serious TEAEs and TEAEs leading to death were somewhat lower in younger (3.4%–5.3% and 0.5%–2.6%, respectively) vs older (5.9%–12.4% and 0%–4.5%) pts. Rates of study drug discontinuation due to TEAEs were similar for older (3.5%) and younger (3.0%) pts with LEF, while rates with MOX were higher in older (7.8%) vs younger (2.4%) pts. CONCLUSIONS: LEF efficacy was high across all age groups, including pts aged ≥85y. The AE profile and study drug discontinuation rates were similar across all age groups. CLINICAL IMPLICATIONS: LEF is a promising new option for treating CABP in pts with advanced age and comorbidities at risk of poor outcomes. DISCLOSURES: Employee relationship with Vir Biotech Please note: >$100000 Added 06/12/2020 by Elizabeth Alexander, source=Web Response, value=Salary Former Employee, Holds Stock relationship with Nabriva Therapeutics Please note: $1001 - $5000 Added 06/12/2020 by Elizabeth Alexander, source=Web Response, value=Company Stock Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 06/01/2020 by Steven Gelone, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 06/01/2020 by Steven Gelone, source=Web Response, value=Ownership interest Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 04/15/2020 by Lisa Goldberg, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: $20001 - $100000 Added 04/15/2020 by Lisa Goldberg, source=Web Response, value=Stock Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 04/08/2020 by Andrew Meads, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: $5001 - $20000 Added 04/08/2020 by Andrew Meads, source=Web Response, value=Shareholder Consultant relationship with Allergan and Nabriva Therapeutics Please note: $1-$1000 Added 04/07/2020 by Christian Sandrock, source=Web Response, value=Consulting fee Removed 04/07/2020 by Christian Sandrock, source=Web Response Consultant relationship with Allergan Please note: $1-$1000 Added 04/07/2020 by Christian Sandrock, source=Web Response, value=Consulting fee Consultant relationship with Nabriva Therapeutics Please note: $1-$1000 Added 04/07/2020 by Christian Sandrock, source=Web Response, value=Consulting fee Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 06/02/2020 by Jennifer Schranz, source=Web Response, value=Salary