A phase 3 trial of Nabriva Therapeutics’ antibiotic lefamulin has met its primary endpoint. The drug held its own against established treatment moxifloxacin, raising hopes that Nabriva can establish it as a first-line monotherapy treatment of community-acquired bacterial pneumonia (CABP).
Investigators enrolled 551 adults with moderate to severe CABP and randomized them to receive either lefamulin—initially intravenously but with the option to switch to oral after three days—or moxifloxacin. People in the moxifloxacin arm suspected of being infected with methicillin-resistant Staphylococcus aureus (MRSA) also received linezolid. Subjects in the lefamulin trial with MRSA got a placebo.
The early clinical response rate for both arms came in at about 90%, with the lefamulin cohort three percentage points lower but still close enough to pass the 12.5% margin for noninferiority. That has encouraged Nabriva to hope lefamulin can secure a prime position in the CABP care pathway.
“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,” Nabriva CEO Colin Broom, M.D., said in a statement.
The trial also cleared the efficacy bar used by European regulators—although lefamulin performed slightly worse numerically again—and the rates of dropouts, treatment-related adverse events and deaths were comparable across the two arms. Some specific adverse events, such as infusion site pain, were more common in the lefamulin arm. But overall the data shared by Nabriva so far suggest safety won’t scuttle lefamulin.
Whether anything else will should become clearer when Nabriva posts data from a second phase 3 trial in the first half of next year. That clinical trial is evaluating an all-oral regimen of the antibiotic in CABP.
Success in that phase 3 would move Nabriva a step closer to establishing lefamulin as a first-line treatment, although it would still need to persuade doctors to prescribe an unfamiliar product that is likely no more effective than well-established treatments.
Such considerations were low on investors’ lists of priorities on Monday. Nabriva moved lefamulin into phase 3 in CABP without having tested it in that indication in smaller clinical trials, making the study something of a punt. The biotech was rewarded with positive data and a 100% increase in its stock.
Nabriva moved into the CABP phase 3 under the guidance of then-CMO Elyse Seltzer, M.D., who joined the company four months before the study was submitted to ClinicalTrials.gov. But Seltzer didn’t stick around to see the success. The former GlaxoSmithKline VP left Nabriva last month, raising ultimately unfounded concerns that the phase 3 trial was headed for disaster.