6/28/23, 10:58 PM LEAP2 Pathway Feedback Search Clinical Topics Home Studies LEAP2 LEAP2 Disease Community-acquired pneumonia Trial question Is oral lefamulin noninferior to moxifloxacin for early clinical response among adults with community- acquired bacterial pneumonia? Study design Multi-center Double blinded RCT Population Characteristics of study participants 48.0% female N = 738 52.0% male 738 patients (351 female, 387 male) Inclusion criteria: adults aged 18 years or older with a Pneumonia Outcomes Research Team (PORT) risk class of II, III, or IV; radiographically documented pneumonia; acute illness; 3 community-acquired bacterial pneumonia symptoms; and 2 vital sign abnormalities Key exclusion criteria: receipt of > 1 dose of a short-acting oral or intravenous antibacterial for CABP within 72 hours before randomization, hospitalization for 2 days within 90 days, confirmed or suspected methicillin-resistant S aureus, being at risk for major cardiac events or dysfunction, and significant hepatic disease Interventions N=370 lefamulin (600 mg PO every 12 hours for 5 days) https://web.pathway.md/studies/recRwIMBMUcv5YGNU 1/2 6/28/23, 10:58 PM LEAP2 Pathway N=368 moxifloxacin (400 mg PO every 24 hours for 7 days) Primary outcome Early clinical response rate at 96 hours after first dose 90.8 % 90.8 90.8 68.1 % 45.4 % Difference not exceeding nonferiority margin 22.7 % 0.0 % Lefamulin Moxifloxacin Difference not exceeding nonferiority margin in early clinical response rate at 96 hours after first dose (90.8% vs. 90.8%; ARD 0.1, 97.5% CI -4.4 to Infinity) Secondary outcomes No significant difference in overall early clinical response by baseline community-acquired bacterial pneumonia pathogen in microbiological intent-to-treat population (90.7% vs. 93%; ARD -2.3, 95% CI -8.2 to 3.5) Safety outcomes No significant differences in serious adverse events, death at 28 days, adverse events leading to discontinuation of study drug or withdrawal from study. Significant differences in diarrhea (12.2% vs. 1.1%), nausea (5.2% vs. 1.9%), vomiting (3.3% vs. 0.8%). Conclusion In adults aged 18 years or older with a Pneumonia Outcomes Research Team (PORT) risk class of II, III, or IV; radiographically documented pneumonia; acute illness; 3 community-acquired bacterial pneumonia symptoms; and 2 vital sign abnormalities, lefamulin was noninferior to moxifloxacin with respect to early clinical response rate at 96 hours after first dose. Reference Elizabeth Alexander, Lisa Goldberg, Anita F Das et al. Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial. JAMA. 2019 Sep 27;322(17):1661-1671. Open reference URL https://web.pathway.md/studies/recRwIMBMUcv5YGNU 2/2