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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File TM Jr, Goldberg L, Das A, Sweeney C, Saviski J, Gelone SP, Seltzer E, Paukner S, Wicha WW, Talbot GH, Gasink LB

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

Clin Infect Dis. 2019 Feb 4. pii: 5306243. doi: 10.1093/cid/ciz090.

PubMed ID
30722059 [ View in PubMed
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Abstract

Background: 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. Methods: 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%). Results: 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. Conclusions: Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated.

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