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Lefamulin found noninferior to moxifloxacin for bacterial pneumonia

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Cost may be a barrier to widespread use

“The development and approval of a new antibiotic is a rare occurrence and a reason to celebrate” given the scientific, regulatory, and economic challenges to antibiotic development, wrote Preeti N. Malani, MD, in an accompanying editorial. Lefamulin in both oral and intravenous forms was approved by the Food and Drug Administration in August 2019 for the treatment of community-acquired bacterial pneumonia, Dr. Malani said.

Lefamulin will likely be an expensive option. According to a manufacturer press release, lefamulin may cost $205/day for intravenous treatment and $275/day for oral treatment. “This is severalfold more than moxifloxacin or levofloxacin, which are the most commonly prescribed fluoroquinolones for CABP [community-acquired bacterial pneumonia],” said Dr. Malani. However, the addition of lefamulin to the array of antibiotics is important because of the persistent burden of bacterial pneumonia as an indication for antibiotic use, Dr. Malani emphasized.

Dr. Malani is affiliated with the University of Michigan, Ann Arbor, and serves as an associate editor of JAMA, but had no financial conflicts to disclose. These remarks were taken from an accompanying editorial (JAMA. 2019 Sep 27. doi:10.1001/jama.2019.16215).



Persistent high rates of bacterial resistance to current treatments have created the need for more options, especially for the treatment of community-acquired bacterial pneumonia (CABP), which remains a leading cause of hospitalization and death in the United States, wrote Elizabeth Alexander, MD, of Nabriva Therapeutics in King of Prussia, Penn., and colleagues. Lefamulin, “the first pleuromutilin antibiotic approved for intravenous and oral use in humans,” has demonstrated activity against many CABP-causing pathogens, including some not susceptible to other classes of antimicrobials, they noted.

Findings of Lefamulin Evaluation Against Pneumonia 2 (LEAP2) were published in JAMA. In this study, the researchers randomized 370 patients to 600 mg of oral lefamulin every 12 hours for 5 days and 368 patients to 400 mg of oral moxifloxacin every 24 hours for 7 days.

Early clinical response rates at 96 hours were 90.8% for both medications (difference of 0.1%). In addition, the rates of clinical response success were similar between the groups in both the modified intent-to-treat population (87.5% with lefamulin and 89.1% with moxifloxacin) and the clinically evaluable population (89.7% with lefamulin and 93.6% with moxifloxacin).

Gastrointestinal issues of diarrhea and nausea were the two most frequently reported treatment-emergent adverse events in both groups. Both conditions occurred more often in the lefamulin group, compared with the moxifloxacin group, but the differences were not significant (12.2% vs. 1.1% and 5.2% vs. 1.9%, respectively).

The study findings were limited by several factors including strict exclusion criteria that may limit the generalizability of the results, as well as a lack of testing for viral copathogens, low recovery of resistant pathogens, and possible misclassification of patient ethnicity, the researchers noted.

However, the results were strengthened by the randomized design, inclusion of patients with more severe CABP, and low rate of discontinuation, they said. The data support previous studies of lefamulin. Its lack of cross-resistance to other drug classes, coverage of typical and atypical CABP pathogens, and options for both oral and intravenous use suggest that it “may provide an alternative approach for the treatment of vulnerable patients,” the researchers said.

The study was supported by Nabriva Therapeutics. Dr. Alexander and several coauthors are employees of Nabriva Therapeutics and own stock in the company.

SOURCE: Alexander E et al. JAMA. 2019 Sep 27. doi:10.1001/jama.2019.15468.

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