EFFICACY AND SAFETY OF LEFAMULIN VS MOXIFLOXACIN FOR ATYPICAL RESPIRATORY PATHOGENS IN ADULTS WITH COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA: POOLED RESULTS FROM THE LEFAMULIN EVALUATION AGAINST PNEUMONIA (LEAP) 1 AND LEAP 2 DOUBLE-BLIND NONINFERIORITY PHASE-3 CLINICAL TRIALS

Abstract

SESSION TITLE: Tuesday Electronic Posters 1 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: Efficacy/safety of lefamulin (LEF), a first-in-class systemic pleuromutilin developed for IV/oral treatment of community-acquired bacterial pneumonia (CABP), was shown in 2 noninferiority phase 3 trials (LEAP 1, LEAP 2). We report LEF efficacy/safety in patients (pts) with atypical respiratory pathogens in pooled LEAP 1/LEAP 2 analyses. METHODS: In LEAP 1, adults with CABP (PORT III–V) received LEF 150mg IV q12h for 5–7d or moxifloxacin (MOX) 400mg IV q24h for 7d, with an optional oral switch (600mg LEF q12h or 400mg MOX q24h). In LEAP 2, adults with CABP (PORT II–IV) received oral LEF for 5d or oral MOX for 7d. Primary endpoints were early clinical response (ECR) at 96±24h after first dose in the intent-to-treat population (ITT, all randomized pts) for the US Food and Drug Administration and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10d after last dose) in the modified ITT (mITT) (received ≥1 dose) and clinically evaluable (met predefined criteria) populations for the European Medicines Agency. Mycoplasma pneumoniae [MP], Legionella pneumophila [LP], and Chlamydophila pneumoniae [CP] were identified at baseline (BL) from pt samples by culture, serology, urinary antigen testing, and real-time PCR. MP and LP isolates were tested for LEF susceptibility by broth microdilution. Analyses herein were done in the microbiologic ITT population (microITT, pts with BL CABP-causing pathogen who received ≥1 dose). RESULTS: In the pooled microITT population (N=709), atypical pathogens were identified in 25.0% (91/364) of LEF-treated pts (PORT II n=26 [28.6%], III n=49 [53.8%], IV n=16 [17.6%]) and 25.2% (87/345) of MOX-treated pts (PORT II n=21 [24.1%], III n=44 [50.6%], IV n=22 [25.3%]). PORT in this subgroup was similar to the overall ITT population (PORT I/II n=376 [29.2%], III n=675 [52.4%], IV/V n=238 [18.5%]). Of pts with MP, LP, and CP, most (71.2% [52/73], 96.9% [63/65], and 79.3% [46/58], respectively) were identified by ≥1 standard diagnostic modality. All 17 cultured MP isolates were susceptible to LEF (MIC50/90=≤0.001/≤0.001μg/mL); the 2 LP isolates were inhibited by 0.5–1μg/mL LEF. In the microITT population, ECR (LEF 85.3%–92.6%, MOX 90.3%–96.8%) and IACR at TOC (LEF 74.1%–89.7%, MOX 74.2%–97.1%) rates in pts with atypical pathogens were high, similar between arms, and consistent with overall pooled results (ECR: LEF 89.3%, MOX 93.0%; IACR: LEF 83.2%; MOX 86.7%). Rates of pts with atypical pathogens with ≥1 treatment-emergent adverse event were 53.8% (49/91) and 66.7% (58/87) in the LEF and MOX groups, respectively. CONCLUSIONS: Short-course LEF therapy (5–7d) for BL atypical pathogens resulted in high ECR responder and IACR success rates in the microITT population and was generally well tolerated. CLINICAL IMPLICATIONS: If approved, LEF may provide a new IV and oral monotherapy alternative to fluoroquinolones and macrolides in pts infected with atypical pathogens. DISCLOSURES: Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/15/2019 by Elizabeth Alexander, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: $20001 - $100000 Added 03/15/2019 by Elizabeth Alexander, source=Web Response, value=stock options Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/14/2019 by Steven Gelone, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/14/2019 by Steven Gelone, source=Web Response, value=Ownership interest Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/14/2019 by Lisa Goldberg, source=Web Response, value=Stock Removed 03/14/2019 by Lisa Goldberg, source=Web Response Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/14/2019 by Lisa Goldberg, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: $20001 - $100000 Added 03/14/2019 by Lisa Goldberg, source=Web Response, value=Stock Grant relationship with Contrafect Please note: $20001 - $100000 Added 03/14/2019 by Gregory Moran, source=Web Response, value=Grant/Research Support Consultant relationship with Allergan Please note: $5001 - $20000 Added 03/14/2019 by Gregory Moran, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Nabriva Please note: $1001 - $5000 Added 03/14/2019 by Gregory Moran, source=Web Response, value=Honoraria Employee relationship with Nabriva Therapeutics Please note: $5001 - $20000 Added 03/15/2019 by Susanne Paukner, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: $5001 - $20000 Added 03/15/2019 by Susanne Paukner, source=Web Response, value=Stocks and stock options Speaker/Speaker's Bureau relationship with Allergan Please note: $20001 - $100000 Added 03/14/2019 by Christian Sandrock, source=Web Response, value=Honoraria Advisory Committee Member relationship with Nabriva Please note: $1001 - $5000 Added 03/14/2019 by Christian Sandrock, source=Web Response, value=Honoraria Employee relationship with UC Davis Please note: >$100000 Added 03/14/2019 by Christian Sandrock, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/07/2019 by Jennifer Schranz, source=Web Response, value=Salary Consultant relationship with Nabriva Please note: $5001 - $20000 Added 03/15/2019 by Andrew Shorr, source=Web Response, value=Consulting fee