LEAP 2 Study Shows Oral Lefamulin Is Safe and Effective in Treatment of Adults with Community-Acquired Bacterial Pneumonia

Conference Correspondent - IDWeek 2018

Lefamulin is a member of the pleuromutilin class of antimicrobials discovered as Staphylococcus aureus inhibitors in 1951.1 In this multicenter, randomized, double-blind, double-dummy study, patients with community-acquired bacterial pneumonia were randomized to oral lefamulin 600 mg every 12 hours for 5 days or oral moxifloxacin 400 mg every 24 hours for 7 days.2 Adults with Pneumonia Patient Outcome Research Team (PORT; a prediction rule used to identify the patients with community-acquired bacterial pneumonia [CABP] who are at low risk for death and other adverse outcomes) Class II-IV3 were eligible (≥50% were to have PORT risk class III or IV). A total of 738 patients were randomized (lefamulin, n = 370; moxifloxacin, n = 368).

The US Food & Drug Administration (FDA) primary end point was early clinical response (ECR; 96 ± 24 hours after first dose) in the intent-to-treat (ITT) population. The European Medicines Agency (EMA) coprimary end points (FDA secondary end points) were investigator assessment of clinical response at test of cure (TOC; 5-10 days after last dose) in the modified ITT and clinically evaluable TOC populations. For FDA and EMA end points, noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval was greater than –10%.

Lefamulin was efficacious regardless of PORT risk class (ECR responder rates for PORT II, III, and IV: 91.8% [168/183], 91.0% [132/145], and 85.0% [34/40] for lefamulin, and 93.1% [176/189], 90.2% [120/133], and 85.7% [36/42] for moxifloxacin, respectively). Both agents showed similar ECR responder and investigator assessment of clinical response success rates across baseline CABP pathogens. Rates of serious adverse events (AEs) and AEs leading to discontinuation were low, and were similar between groups. Most frequently reported AEs were gastrointestinal, the majority of which were mild in severity, with few treatment discontinuations.

Five-day oral lefamulin therapy demonstrated noninferiority for both FDA and EMA efficacy end points versus 7-day oral moxifloxacin. Both agents were safe and generally well-tolerated.

References

  1. Eyal Z, et al. Sci Rep. 2016;6:39004.
  2. Alexander E, et al. IDWeek 2018. Abstract LB6.
  3. Fine MJ, et al. N Engl J Med. 1997;336:243-250.
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