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), released by biopharmaceutical company, Nabriva Therapeutics. Lefamulin was found non-inferior to moxifloxacin for an early clinical response (ECR) in patients with CABP.
Two pivotal Phase 3 trials have been completed evaluating the safety and efficacy of lefamulin for the treatment of adults with CABP. In their first clinical trial in patients with CABP (LEAP-1), seven-days of intravenous (IV) to oral lefamulin in adults with moderate to severe CABP was compared to moxifloxacin (IV/oral), with or without linezolid. In the LEAP 2 trial, five-days of oral lefamulin was compared to seven-days of oral moxifloxacin in adults with moderate CABP. Both trials were multi-center, randomized, controlled and double-blind. Lefamulin met all FDA and EMA primary endpoints in both LEAP 1 and LEAP 2 and was shown to be generally well tolerated
LEAP 2 evaluated the safety and efficacy of 5 days of oral lefamulin compared to 7 days of oral moxifloxacin in adult patients with moderate community-acquired bacterial pneumonia (CABP). In September 2017, the company announced positive results from its first Phase 3 clinical trial, in which intravenous (IV) to oral lefamulin was found to be non-inferior to IV to oral moxifloxacin with or without linezolid.
LEAP 2 was a global, randomized, double-blind, double-dummy trial that compared the efficacy and safety of 600 mg of oral lefamulin twice a day for 5 days versus 400 mg of oral moxifloxacin once daily for 7 days in 738 patients (370 in the lefamulin arm and 368 in the moxifloxacin arm). The lefamulin arm enrolled 183 (49.5%), 145 (39.2%) and 40 (10.8%) patients with a Pneumonia.
In this trial, lefamulin was generally well tolerated. In LEAP 2, lefamulin met the U.S. Food and Drug Administration (FDA) primary endpoint of non-inferiority compared to moxifloxacin for an early clinical response (ECR) assessed 72 to 120 hours following initiation of therapy. ECR was 90.8% for the 5-day treatment course of lefamulin and 90.8% for the 7-day treatment course of moxifloxacin.
The rate of treatment-emergent adverse events (TEAEs) was 32.6% in the lefamulin arm and 25.0% in the moxifloxacin arm. A low percentage of patients discontinued study drug in the lefamulin arm (6.8%) and in the moxifloxacin arm (7.6%). TEAEs leading to discontinuation of study drug were uncommon and were observed in 3.0% of patients in the lefamulin arm and 2.2% of patients in the moxifloxacin arm.
Adverse events reported were diarrhea/loose stools, nausea, vomiting, hypertension, headache, gastritis and urinary tract infection.
Further analysis of the LEAP 2 trial results including analysis of additional patient population groups in the trial and secondary and exploratory endpoints related to these population groups is ongoing.
“Coupled with our successful LEAP 1 trial, the positive results from LEAP 2 suggest lefamulin could be an excellent empiric treatment option for patients with CABP and help address the problem of antibiotic resistance. With these LEAP 2 results, we believe there is a significant opportunity for oral lefamulin as a 5-day treatment option for CABP in the community,” said Dr. Colin Broom, the chief executive officer of Nabriva Therapeutics