LEAP 2 study demonstrates safety, efficacy of oral lefamulin for CABP

Issue: November 2018

SAN FRANCISCO — A 5-day course of oral lefamulin is noninferior to 7 days of oral moxifloxacin for the treatment of community-acquired bacterial pneumonia, according to results from a second phase 3 trial presented at IDWeek.

“Lefamulin is a first-in-class pleuromutilin for human systemic use in serious bacterial infections,” Jennifer Schranz, MD, chief medical officer for Nabriva Therapeutics, told Infectious Disease News. “It’s the first new class that’s been discovered for treatment of community-acquired bacterial pneumonia (CABP) in over 20 years.”

The phase-3 LEAP 1 trial demonstrated that IV to oral lefamulin for CABP was noninferior to IV to oral moxifloxacin, with or without linezolid added to moxifloxacin for suspected MRSA. Additionally, in May, Nabriva announced positive topline results from a second phase 3 trial, LEAP 2, reporting that the investigational antibiotic met the FDA and European Medicines Agency (EMA) noninferiority endpoints.

The findings presented at IDWeek were from LEAP 2, a multicenter, randomized, double-blind, double-dummy trial. The study enrolled 738 patients with CABP, with 370 receiving 600 mg of oral lefamulin twice daily for 5 days and 368 receiving 400 mg of moxifloxacin once daily for 7 days. Eligible participants were adults with a Pneumonia Outcomes Research Team (PORT) risk class of at least 2 and no higher than 4.

The FDA primary endpoint was early clinical response in the intent-to-treat (ITT) population. The FDA secondary endpoint and the EMA primary endpoint was investigator assessment of clinical response at test of cure (TOC) 5 to 10 days after the last dose was administered in the modified ITT (mITT) and clinically evaluable TOC populations.

Schranz and colleagues reported that the 5-day course of lefamulin met the FDA and EMA primary endpoints, demonstrating noninferiority to 7 days of moxifloxacin. The agents demonstrated high response rates, with both reaching 90.8% early clinical response in ITT. Regardless of PORT risk class, lefamulin was found to be efficacious. Early clinical response rates were 91.8%, 91% and 85% for PORT classes 2, 3 and 4, respectively. Patients receiving moxifloxacin with a PORT class of 2, 3 or 4 demonstrated early clinical response rates of 93.1%, 90.2% and 85.7%, respectively.

Schranz and colleagues observed similar success rates of early clinical response and investigator assessment of clinical response for both lefamulin and moxifloxacin across baseline CABP pathogens. The investigator assessment of clinical response in the mITT population was 87.5% for lefamulin and 89.1% for moxifloxacin. Investigator assessment of clinical response in the clinically evaluable TOC population was 89.7% for lefamulin and 93.1% for moxifloxacin. Furthermore, both treatment groups reported low rates of serious adverse events, as well as low rates of study discontinuation because of adverse events. Gastrointestinal symptoms, such as diarrhea, nausea and vomiting, were the most frequently reported adverse events, according to Schranz.

“What’s really important about lefamulin as a new class is that it allows us the flexibility to treat IV to oral or oral only, with the efficacy of a respiratory fluoroquinolone but be fluoroquinolone-sparing because of safety concerns identified with this class,” Schranz said. “This allows physicians the option of a monotherapy antibiotic regimen with complete spectrum of activity, including against resistant pathogens for CABP.” – by Marley Ghizzone

Reference:

Alexander E, et al. Abstract LB6. Presented at: IDWeek; Oct. 3-7, 2018; San Francisco.

Disclosures: Schranz is an employee and shareholder at Nabriva Therapeutics receiving salary and stock options. Please see the study for all other authors’ relevant financial disclosures.