699. Hepatobiliary Safety in Adults With Community-Acquired Bacterial Pneumonia (CABP) Treated With Lefamulin (LEF) or Moxifloxacin (MOX): Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Results

BACKGROUND: LEF efficacy and safety were shown in 2 noninferiority trials (LEAP 1/2) vs. MOX in adults with CABP. We assessed the hepatobiliary safety of LEF based on pooled analyses of LEAP 1/2 data. METHODS: In LEAP 1, PORT III–V patients received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF 600 mg q12h for 5 days or oral MOX 400mg q24h for 7 days. Exclusion criteria included infection with HBV/HCV, acute hepatitis, cirrhosis, AST or ALT >5xULN, total bilirubin >3xULN (unless Gilbert’s disease), AST or ALT >3xULN and total bilirubin >2xULN, and manifestation of end-stage liver disease. Hepatic safety was assessed from baseline (BL) and multiple post-BL blood samples using a central laboratory, TEAEs, and expert consultant adjudication. Pooled analyses included all randomized/treated patients (safety population). RESULTS: Of 1282 randomized/treated patients, 1251 had BL and post-BL hepatobiliary data (table). Post-BL distribution of ALT/AST was generally similar for both groups, although ALT >AST in the absence of muscle injury or alcohol use. Overall, rates of patients experiencing an increase in ALT/AST >3xULN, ALP >2xULN, or total bilirubin >1.5xULN were low (table). Patients with elevated vs. normal BL transaminases (TAs) were more likely to have post-BL elevations >3xULN, but the vast majority remained <5xULN. Among patients with ALT >5xULN, peak increases were generally seen in the first week after the first LEF dose and declined to within/near normal levels by late follow-up (day 28); for MOX, time to peak ALT was less consistent (figure). No LEF pt and 1 MOX pt met laboratory criteria for Hy’s Law. Elevations in TAs were reversible, with no evidence of chronic injury. The LEF injury pattern was predominantly hepatocellular (50.0%)/mixed (40.0%), with no apparent gender, age, or ethnic predominance. TEAEs in the hepatobiliary disorders system organ class were reported in 6 (0.9%) LEF patients and 6 (0.9%) MOX patients, with similar levels seen in patients with elevated BL TAs. There were no symptomatic patients, severe disease, or evidence of hypersensitivity. CONCLUSION: Low incidences of hepatobiliary parameter elevations and TEAEs were observed, with no apparent differences between LEF and MOX. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.