Lefamulin scores again in multilobar pneumonia

The pleuromutilin inhibitor lefamulin shows similarly high efficacy as moxifloxacin (a standard fluoroquinolone therapy for clearing bacterial pneumonia) regardless of whether it was for unilobar or multilobar pneumonia, according to pooled data of the LEAP* 1 and 2 studies.  

“Pneumonia with multilobar infiltration is associated with early treatment failure, delayed resolution, and prolonged hospitalization,” explained presenting author Dr Thomas File of Summa Health in Akron, Ohio, Texas, US during a presentation at CHEST 2021 Congress.

Lefamulin is the first-in-class pleuromutilin inhibitor to be approved for systemic use in humans. It has been authorized for intravenous (IV) as well as oral use to treat adults with community-acquired bacterial pneumonia (CABP), based on noninferiority findings in head-to-head comparison against moxifloxacin in the phase III LEAP 1 and 2 trials.

LEAP-1 randomized 551 adult patients with CABP (PORT risk classes III-V) to IV lefamulin or moxifloxacin, both with an option to switch to oral dosing. LEAP-2 (n=738) had similar design except disease was generally milder (PORT risk classes II-IV) and both drugs were administered orally throughout. [CHEST 2021;doi:10.1016/j.chest.2021.07.510]

A total of 676 patients who had radiologically confirmed unilobar infiltrates (n=468) or multilobar (n=208) were pooled from the two trials for the current analysis. Approximately half of them had PORT class III pneumonia.

Compared with patients with unilobar infiltrates, those with multilobar pneumonia were older (37 percent vs 47 percent were aged ≥65 years), more likely to be in PORT risk class IV–V (16 percent vs 25 percent), had prior asthma/chronic obstructive pulmonary disease (16 percent vs 21 pecent), or history of smoking (41 percent vs 47 percent) — in keeping with previosu observations that multilobar disease had worse prognosis.

Despite this, both lefamulin and moxifloxacin showed similarly high early clinical response rates regardless of whether patients had unilobar (92 percent vs 94 percent) or multilobar pneumonia (85 percent vs 90 percent).  

The rates of investigator assessment of clinical response (IACR) were also similarly high between the lefamulin and the moxifloxacin arms for both unilobar (86 percent vs 89 percent) and multilobar pneumonia (77 percent vs 80 percent).

“Lefamulin efficacy was high for patients with unilobar or multilobar pneumonia and comparable to that with moxifloxacin,” File stated. “Lefamulin is an alternative to fluoroquinolones for treating CABP in patients with multilobar pneumonia who have or may be at risk for severe pneumonia.”

In addition, the profile of treatment-emergent adverse events (TEAEs) was similar in both treatment groups, he noted. Gastrointestinal events were the most common TEAEs across both groups, with similar rates in the lefamulin-treated patients (14 percent and 10 percent for unilobar and multilobar disease, respectively) and moxifloxacin-treated patients (9 percent and 11 percent for unilobar and multilobar disease, respectively).

*LEAP: Lefamulin Evaluation Against Pneumonia