LEAP 2: Oral Lefamulin Demonstrates Favorable Safety, Tolerability for Patients With CABP
Lefamulin demonstrated non-inferiority when compared with moxifloxacin, and both treatment arms reported a low rate of serious treatment-emergent AEs or treatment-emergent AEs leading to discontinuation.
Intravenous (IV) to oral lefamulin was found to be generally safe and well-tolerated for the treatment of community acquired bacterial pneumonia (CABP) in the phase 3 LEAP 1 trial. In LEAP 2, lefamulin again successfully met the US Food and Drug Administration (FDA) primary endpoint of non-inferiority compared with moxifloxacin for early clinical response, which was evaluated in the intent-to-treat patient population 72 to 120 hours after treatment was initiated.
Investigators presented new LEAP 2 safety and tolerability data on oral lefamulin at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2019), where Contagion® caught up with Jennifer Schranz, MD, chief medical officer with Nabriva Therapeutics, to discuss the research (see video).
The novel pleuromutilin antibiotic was tested in a multi-center, double-blind, double-dummy study (NCT02813694; EudraCT 2015-004782-92), which randomized 738 patients with CABP (PORT risk class II—IV) to receive either oral lefamulin (n = 370; 600 mg lefamulin once every 12 hours for 5 days) or oral moxifloxacin (n = 368; 400 mg moxifloxacin every 24 hours for 7 days). The research team evaluated the rate of treatment-emergent adverse events (AEs), laboratory results, 12-lead electrocardiograms, and 28-day all-cause mortality.
Lefamulin demonstrated non-inferiority when compared with moxifloxacin, and both treatment arms reported a low rate of serious treatment-emergent AEs or treatment-emergent AEs leading to discontinuation. Gastrointestinal (GI) treatment-emergent AEs were the most common with lefamulin compared with moxifloxacin (17.9% vs 7.6%). Diarrhea and nausea were the most common GI symptoms reported, though no case was severe enough to lead to study drug discontinuation.
One case of Clostridium difficile was noted during an extended hospital stay in a patient successfully treated with lefamulin. Low rates of hepatobiliary treatment-emergent AEs (1.1% lefamulin, 0.5% moxifloxacin) and cardiac treatment-emergent AEs (2.2% lefamulin, 2.4% were reported.
Increases in Fridericia's Correction Formula (QTcF) interval >60 msec postbaseline occurred in 4 lefamulin and 7 moxifloxacin patients. No patients met Hy’s Law criteria.
Investigators concluded that oral lefamulin monotherapy is generally safe, well-tolerated, and produced a low discontinuation rate due to treatment-emergent AEs.
“The majority of GI events were mild, rarely led to discontinuation, and occurred more commonly with lefamulin than moxifloxacin,” the team wrote in the abstract. “This contrasts with the IV-to-oral switch profile in which higher rates of GI events occurred with moxifloxacin. These results add to the developing favorable safety/tolerability profile of IV and oral lefamulin.”
In February, the US Food and Drug Administration accepted the New Drug Applications for both the oral and intravenous (IV) formulations of lefamulin for the treatment of CABP. The Prescription Drug User Fee Act goal date for the completion of the FDA’s review is August 19, 2019.
The study, “Oral Lefamulin Demonstrates Favorable Safety and Tolerability in Adults with Community-Acquired Bacterial Pneumonia in the Phase III Lefamulin Evaluation Against Pneumonia (LEAP 2) Study,” was presented as a mini oral e-poster on Tuesday, April 16, 2019, at ECCMID 2019 in Amsterdam, the Netherlands.