This article is more than 5 years old. Information may no longer be current.
Lefamulin effective against bacterial pneumonia in phase 3 trial
Click Here to Manage Email Alerts
Lefamulin, a novel antibiotic being developed by Nabriva Therapeutics, was effective in a global phase 3 trial investigating its use in patients with community-acquired bacterial pneumonia, or CABP, the leading cause of infectious death in the United States.
According to Nabriva, in patients with CABP, lefamulin met the FDA’s primary endpoint of a noninferiority margin of 12.5% in early clinical response (ECR) assessed 72 or 120 hours after initiation of therapy in the intent-to-treat (ITT) population compared with moxifloxacin with or without adjunctive linezolid.
The trial, named LEAP 1, compared the efficacy and safety of IV to oral lefamulin with IV to oral moxifloxacin, with or without linezolid. It was the first of two phase 3 clinical trials investigating the new drug. The company said it expects topline results from LEAP 2 — an ongoing second global phase 3 trial comparing oral lefamulin with moxifloxacin in patients with moderate CABP — to be available in the first quarter of 2018.
“Community-acquired bacterial pneumonia is a common and potentially life-threatening illness for which presently available recommended antimicrobials have potential limitations often associated with resistance or safety,” Thomas M. File Jr., MD, an infectious disease specialist at Northeast Ohio Medical University and Summa Health and an Infectious Disease News Editorial Board member, said in a news release.
“With bacterial resistance continuing to increase, patients and physicians are in need of new safe and effective treatment options that adhere to the principles of antibiotic stewardship. These positive topline results evaluating the efficacy and safety of lefamulin in patients with community-acquired bacterial pneumonia are promising.”
Nabriva said that lefamulin, a pleuromutilin antibiotic, “is the first antibiotic with a novel mechanism of action to have reached late-stage clinical development in more than a decade.”
In the phase 3 trial, 551 patients were randomly assigned to receive 150 mg of IV lefamulin every 12 hours or 400 mg of IV moxifloxacin daily. Linezolid — or matching placebo for patients in the lefamulin arm — could be added to treatment if an investigator suspected that a patient was infected with MRSA before being randomly assigned to a treatment. Moxifloxacin is not approved to treat MRSA.
During the trial, investigators had the option to switch patients to oral therapy after 3 days or at least six doses of IV therapy. Those patients received a 600-mg lefamulin tablet every 12 hours or 400 mg of moxifloxacin daily and 600 mg linezolid every 12 hours if needed.
Among 276 patients assigned lefamulin, ECR rates were 87.3% compared with 90.2% in the 275 patients in the moxifloxacin arm, a treatment difference of –2.9 percentage points (95 CI, –8.5 to 2.8), according to the release.
The rate of treatment-emergent adverse events (TEAEs) was similar in both arms, 38.1% vs. 37.3%, the company said. Moreover, the rates of TEAEs leading to study drug discontinuation were 2.9% vs. 4.4%, and the rates of withdrawal from the trial were 1.8% vs. 4% in the lefamulin and moxifloxacin arms, respectively. Nabriva said lefamulin also met the primary endpoints set by the European Medicines Agency.
Nabriva CEO Colin Broom, MBBS, said the data “provide strong evidence of the potential of lefamulin to treat adults with CABP and provide an alternative to a current gold standard treatment regimen.”
“Due to lefamulin’s flexible dosing and targeted spectrum of activity against the pathogens most commonly associated with CABP, including multidrug-resistant strains, we believe that lefamulin is well-suited to be a first-line empiric monotherapy,” he said in the release.
Reference:
Nabriva Therapeutics. Nabriva Therapeutics announces positive topline results from global, phase 3 clinical trial evaluating IV and oral lefamulin for the treatment of community-acquired bacterial pneumonia. 2017. https://globenewswire.com/news-release/2017/09/18/1124000/0/en/Nabriva-Therapeutics-Announces-Positive-Topline-Results-from-Global-Phase-3-Clinical-Trial-Evaluating-IV-and-Oral-Lefamulin-for-the-Treatment-of-Community-Acquired-Bacterial-Pneumo.html. Accessed September 18, 2017.
Disclosures: Broom is the CEO of Nabriva. File has worked as an investigator and consultant for Nabriva.