Lefamulin safe, effective monotherapy alternative for older adults with CABP
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Lefamulin demonstrated high early clinical response and was safe in patients with community-acquired bacterial pneumonia with advanced age and comorbidities, according to a post hoc, pooled analysis of the LEAP 1 and LEAP 2 trials.
Lefamulin (Xenleta, Nabriva Therapeutics) is a first-in-class pleuromutilin antibiotic that is FDA approved for IV and oral use in adults with community-acquired bacterial pneumonia (CABP). Efficacy and safety of lefamulin were previously demonstrated in the noninferiority phase 3 LEAP 1 and LEAP 2 trials. At the virtual CHEST Annual Meeting, researchers reported findings from a pooled analysis of the LEAP 1 and LEAP 2 data on efficacy and safety outcomes by age group.
“People of advanced age are especially at risk for developing CABP as a result of a weakened immune system and age-related comorbidities that increases the changes of hospitalization and CABP-related complications leading to functional impairment and/or mortality,” Jennifer Schranz, MD, Chief Medical Officer of Nabriva, stated in a company press release. “Our post-hoc analysis highlights that Xenleta provides a safe and effective empiric monotherapy alternative to fluoroquinolones for treatment of CABP in patients with advanced age and comorbidities.”
In the pooled analysis of 1,289 patients from LEAP 1 and LEAP 2, 646 were randomly assigned IV or oral lefamulin and 643 were randomly assigned moxifloxacin.
Forty percent of patients were aged older than 65 years (mean age, 58 years). Patients were predominantly male (55%) and white (79.3%). Compared with younger patients, those aged 65 years and older were more likely to have higher pneumonia severity scores and comorbidities including moderate or severe renal impairment, cardiac disease, hypertension, diabetes, and asthma and/or chronic obstructive pulmonary disease.
Across all age groups, the researchers reported high and similar early clinical response rates — 88% with lefamulin and 82% with moxifloxacin — including in patients aged older than 85 years (88.5% and 82.5%, respectively). In addition, investigator assessment of clinical response at the test of cure were high and similar in all age groups in the modified intent-to-treat population ( 82% and 83%, respectively) and the clinically evaluable population ( 86% and 88%, respectively), according to the abstract.
In other results, the adverse event profile and study drug discontinuation rates were similar across all age groups. Rates of serious treatment-emergent adverse events and treatment-emergent adverse events leading to death in those assigned lefamulin were lower in younger patients (3.4% to 5.3% vs. 0.5% to 2.6%) vs. older patients (5.9% to 12.4% vs. 0% to 4.5%). Rates of study drug discontinuation due to treatment-emergent adverse events were similar for older (3.5%) and younger (3%) patients with lefamulin. The most common adverse events were gastrointestinal, and were similar across age groups that received lefamulin (8.6% to 15%), according to new results.
“Lefamulin has demonstrated high early clinical response and investigator-initiated or assessed clinical response success rates in all groups, particularly in patients greater than 85 [years of age],” Christian Sandrock, MD, pulmonary critical care physician at the University of California, Davis, said during a poster presentation. “The safety and tolerability was stable across all three age groups and similar to the comparator moxifloxacin, which really provides that lefamulin is a safe and effective monotherapy alternative when compared to fluoroquinolones in the treatment of community-acquired pneumonia in patients with advancing age and comorbidities.”
Healio previously reported results of the LEAP 1 and LEAP 2 trials. See coverage here and here. In LEAP 1, patients were randomly assigned to receive lefamulin 150 mg IV every 12 hours for 5 to 7 days or moxifloxacin 400 mg IV every 24 hours for 7 days, with the option to switch to oral therapy after six IV doses of study drug if predefined improvement criteria were met. In LEAP 2, patients were randomly assigned to receive oral lefamulin 600 mg every 12 hours for 5 days or oral moxifloxacin 400 mg every 24 hours for 7 days.