Nabriva lines up FDA filing after antibiotic clears second pivotal test

A second phase 3 trial of Nabriva Therapeutics’ lefamulin has hit its primary endpoint. The positive readout further burnishes the prospects of the antibiotic, which is set to go before the FDA later this year.

Nabriva’s second trial compared an oral, five-day lefamulin regimen to seven days of treatment with approved antibiotic moxifloxacin in patients with moderate community-acquired bacterial pneumonia (CABP). The trial associated the regimens with identical early clinical response rates of 90.8%, resulting in it hitting its noninferiority primary endpoint. The study also cleared European regulators’ efficacy bar.

With the positive efficacy data coming eight months after an intravenous-to-oral regimen hit the mark in the first phase 3, Nabriva has the results to file for FDA approval of lefamulin in the fourth quarter. 

If lefamulin gets past the FDA, Nabriva will then face the challenge of getting payers and doctors to switch to the drug. Cheap generic antibiotics with comparable efficacy to lefamulin are already on the market. But Nabriva nonetheless thinks lefamulin can carve out a spot as first-line option.

“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 last fall.  

The positive efficacy readout was marred slightly by the safety data. Twelve percent of patients in the lefamulin arm suffered from diarrhea, as compared to 1% in the moxifloxacin cohort. Most of the cases were mild, though, with the remaining 29% classed as moderate. In the previous phase 3, 0.7% of patients in the lefamulin arm had diarrhea, as compared to almost 8% in the moxifloxacin group.

Other aspects of the data were also worse in the second study. Notably, investigators saw one case of Clostridium difficile infection in the second trial. The patient initially responded positively to lefamulin but was later diagnosed with the infection during an extended hospital stay. No cases of C. difficile infection occurred in the first phase 3. 

Shares in Nabriva rose 20% in premarket trading.