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Clin Infect Dis. 2019 Feb 4. doi: 10.1093/cid/ciz090. [Epub ahead of print]

Efficacy and Safety of IV-to-Oral Lefamulin, a Pleuromutilin Antibiotic, for Treatment of Community-Acquired Bacterial Pneumonia: The Phase 3 LEAP 1 Trial.

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Summa Health, Akron, OH, USA.
Nabriva Therapeutics US, Inc., King of Prussia, PA, USA.
Das Consulting, Guerneville, CA, USA.
Urogen Pharma, New York, NY, USA.
Nabriva Therapeutics GmbH, Vienna, Austria.
Talbot Advisors LLC, Anna Maria, FL, USA.



Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study (NCT02559310) was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP.


In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin 150 mg intravenously (IV) q12h or moxifloxacin 400 mg IV q24h. After 6 doses, patients could be switched to oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US FDA primary endpoint was early clinical response (ECR) 96±24 hours after the first dose of study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The EMA co-primary endpoints were investigator assessment of clinical response (IACR) 5-10 days after last dose of study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%).


551 patients were randomized (n=276 lefamulin; n=275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%; difference: -2.9% [95% confidence interval: -8.5, 2.8]) and IACR (mITT, 81.7% vs 84.2%; difference -2.6% [-8.9, 3.9]; CE, 86.9% vs 89.4%; difference -2.5% [-8.4, 3.4]). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin.


Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated.


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