Nabriva Therapeutics plans to file a New Drug Application with the FDA in the fourth quarter of 2018.
The clinical-stage biopharmaceutical company, Nabriva Therapeutics, released positive top-line results from the second global phase 3 clinical trial of lefamulin, for the treatment of adults with community-acquired bacterial pneumonia (CABP).
“Today marks an exciting advance in the treatment of CABP as we are one step closer to potentially making a much-needed new class of antibiotic available to patients and health care providers,” Nabriva’s chief medical officer Dr. Jennifer Schranz, said in a recent statement.
Lefamulin works by adhering to the peptidyl transferase center on the bacterial ribosome in a way that interferes the interaction of protein production at 2 key sites, leading to “the inhibition of bacterial proteins and the cessation of bacterial growth,” according to Nabriva.
The trial, dubbed Lefamulin Evaluation Against Pneumonia (LEAP 2), is the second of 2 global, pivotal phase 3 clinical trials which set out to assess the safety and efficacy of the semi-synthetic compound.
Last year, the company announced positive results from the first phase 3 trial, LEAP 1, where intravenous to oral lefamulin met the US Food and Drug Administration (FDA) primary endpoint of non-inferiority compared with moxifloxacin with or without adjunctive linezolid.
In LEAP 2, lefamulin again successfully met the FDA primary endpoint of non-inferiority (NI, 10% margin) compared with moxifloxacin for early clinical response (ECR), which was evaluated in the intent to treat (ITT) patient population 72 to 120 hours after treatment was initiated. The investigators on the trial found that ECR was 90.8% for just 5 days of treatment with lefamulin, whereas ECR was 90.8% for 7 days of treatment with moxifloxacin (treatment difference 0.1 [95% confidence interval (CI) -4.4, 4.5]), according to a recent press release.
Lefamulin also met the European Medicines Agency (EMA) primary endpoint for non-inferiority (NI, 10% margin) compared with moxifloxacin, according to investigator assessment of clinical response (IACR) which occurred in the modified intent to treat (mITT) and clinically evaluable test of cure (CE-TOC) patient populations 5 to 10 days after the study was completed.
For the mITT population, IACR rates were 87.5% for those who received lefamulin compared with 89.1% for those who received moxifloxacin. IACR rates for those in the CE-TOC population were 89.7% for lefamulin compared with 93.6% for moxifloxacin.
“Lefamulin has the potential to be the first-in-class pleuromutilin antibiotic available for IV or oral administration, and results from LEAP 2 provide additional evidence of its efficacy and tolerability in the treatment of adults with CABP,” Dr. Schranz is quoted as saying. “We believe lefamulin is well-suited for the empiric treatment of CABP given its short-course regimen, a novel mechanism of action, a targeted spectrum of activity against the most common and problematic CABP pathogens, and its safety and tolerability profile.”
Pleuromutilin antibiotics are thought to work against pathogens that have previously thwarted other treatment regimens, which is especially important in light of a report from the US Centers for Disease Control and Prevention that in 30% of cases, pneumococcal bacteria are resistant to 1 or more antibiotics.
“As bacterial resistance continues to increase, there is an urgent need for new, safe, and effective IV and oral treatment options for CABP,” Andrew Shorr, MD, MPH, MBA, section head of Pulmonary and Critical Care Medicine at MedStar Washington Hospital Center, said in a recent statement. “The positive topline results from LEAP 1 and LEAP 2 indicate that lefamulin could provide health care providers with a new potential option in the treatment of CABP across the spectrum of care, ranging from the hospital to the community.”
Based on the positive results found in the LEAP 1 and LEAP 2 trials, Nabriva plans to file a New Drug Application to the FDA in the fourth quarter of 2018 for lefamulin.