Efficacy and safety of lefamulin in chinese adults with community-aquired bacterial pneumonia (cabp): results of lefamulin evaluation against pneumonia (leap-china) study

SESSION TITLE: Pneumonia: New Drugs, Old Bugs, and Other Things for Your Consideration SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/10/2023 12:55 pm - 01:40 pm PURPOSE: New treatment options for CABP with promising activity and improved tolerability are needed. Lefamulin, a new pleuromutilin antibiotic agent, is active against common CABP pathogens. The third of 3 phase III Lefamulin Evaluation Against Pneumonia studies, LEAP-China (CTR20191226) is a multicenter, randomized, double-blind, bridging trial to assess the efficacy, safety of lefamulin in Chinese adults with CABP. It was designed to show consistency with LEAP 1, an IV-to-oral switch study in patients with PORT Risk Class III-V. METHODS: Adults with CABP were randomized 2:1 to receive lefamulin 150 mg IV Q12 hours or moxifloxacin 400 mg IV Q24 hours. Qualifying patients could be switched to oral therapy after 6 doses. The primary endpoints included investigator assessment of clinical response (IACR) in modified intent-to-treat (mITT) population at test of cure (TOC, 5-10 days after last dose of study drug). Early clinical response (ECR) at 96 hours (within 24-hour window) after receipt of first drug dose in the intent-to-treat (ITT) population and IACR of clinically evaluable (CE) population at TOC were included in the secondary endpoints. For the primary endpoints, consistency was concluded if the point estimate was >-12.5% for the difference between the two groups. RESULTS: There were 124 patients randomized (n = 82 lefamulin; n = 42 moxifloxacin) in the mITT population. The rates of IACR at TOC were 76.8% (63/82) with lefamulin vs 71.4% (30/42) with moxifloxacin in mITT population (difference 5.4%, 95% CI: -12.8 to 23.6). The point estimate of differences between the treatment groups surpassed the established objective of -12.5%, which demonstrated consistency with results of LEAP 1 study and the success of bridging. Similar rates of IACR at TOC were recorded for CE population (86.0% [49/57] with lefamulin vs 86.2% [25/29] with moxifloxacin; difference -0.2%, 95% CI: -18.3 to 17.8). The ECR responder rates in ITT population were 60.2% (50/83) with lefamulin vs 64.3% (27/42) with moxifloxacin (difference -4.0%, 95% CI: -23.7 to 15.7). Both agents demonstrated similar ECR responder and IACR success rates across baseline CABP pathogens. Rates of serious adverse events (SAEs) were 3.7% for lefamulin and 9.5% for moxifloxacin. Most frequently reported treatment-emergent adverse events (TEAEs) were infusion site reactions, the majority of mild severity with no discontinuation. CONCLUSIONS: This bridging trial met the consistency criteria with LEAP 1, supporting the noninferiority conclusion of lefamulin to moxifloxacin. The frequency of TEAEs was comparable between the two groups. CLINICAL IMPLICATIONS: Lefamulin is a promising new option as empirical monotherapy for Chinese adults with CABP. DISCLOSURES: No relevant relationships by Haihui Huang No relevant relationships by Rae Yuan No relevant relationships by Yingyuan Zhang No disclosure on file for Jie Ding No disclosure on file for Hirokazu Matsukami