Delafloxacin Noninferior to Moxifloxacin for CABP in Phase 3 Study

As pathogens become more resistant and the population ages, the burden of community acquired bacterial pneumonia (CABP) continues to increase. In October 2019, the US Food and Drug Administration approved delafloxacin (Baxdela) as a new option for the treatment of CABP.

The FDA’s approval was based upon results of a study of a phase 3 study which have now been made available in full and published in Open Forum Infectious Diseases.

The study comparing the drug to demonstrated that delafloxacin is well tolerated and effective in adults with CABP, with coverage of gram-positive, gram-negative, and atypical pathogens.

The study was conducted by an international team of experts from Universitat Autònoma de Barcelona, Case Western Reserve University, University Hospital la Paz, Victor Babes Clinical Hospital of Infectious Diseases and Pneumophtisiology, Melinta Therapeutics, and Firma Clinical Research.

The investigators performed a randomized, double-blind, comparator-controlled, multicenter, global study comparing the efficacy and safety of delafloxacin 300 mg twice daily to moxifloxacin 400 mg 4 times daily for adults with CABP.

The study enrolled 859 participants, 431 of whom were randomized to the delafloxacin group and 428 were randomized to the moxifloxacin group. Median duration of intravenous and oral treatment was 9 days in both groups.

The primary end point of the study was early clinical response, defined as improvement at 96 (+/- 24) hours after first dose.

Improvement was assessed according to the US Food and Drug Administration standard of improvement in at least 2 of the following symptoms: frequency or severity of cough, amount and quality of productive sputum, chest pain, dyspnea, and no worsening of the other symptoms in the intent-to-treat population.

Investigators also assessed clinical response at test of cure and microbiologic response.

In the intent-to-treat analysis population, early clinical response rates were 88.9% in the delafloxacin group and 89% in the moxifloxacin group. Based on this, delafloxacin was found noninferior to moxifloxacin.

At test of cure, success rates were 90.5% in the delafloxacin group and 89.7% in the moxifloxacin group.

While outcomes were similar between most subgroups analyzed, investigators did note 1 exception.

“Responder rates were similar between the delafloxacin and moxifloxacin groups for all subgroups analyzed except for subjects with COPD [chronic obstructive pulmonary disease] or asthma, where delafloxacin was significantly better than moxifloxacin,” study authors wrote.

In microbiologic analysis of a modified-intent-to-treat population, investigators found that delafloxacin exhibited at least 16-fold greater activity than moxifloxacin against gram-positive and fastidious gram-negative pathogens.

Treatment emergent adverse events considered potentially related to the study drug occurred in 65 participants in the delafloxacin group and 54 participants in the moxifloxacin group. Investigators classified these events as mostly mild in severity.

In the delafloxacin group, 2 participants had treatment emergent adverse events considered both severe and potentially related to the study drug.

“Delafloxacin has the fluoroquinolone class safety warnings, but the unique attributes of delafloxacin may also offer a differentiated AE [adverse event] profile compared to other fluoroquinolones, primarily lack of QTc prolongation, phototoxicity and major central nervous system events,” authors of the study wrote.

Overall, the study authors concluded that delafloxacin was effective and well tolerated, providing a treatment option that offers patients simple and continuous treatment out of the hospital setting.