Second Phase III trial of Baxdela (delafloxacin) success in treatment of acute bacterial skin and skin structure infections,- Melinta Therapeutics

Melinta Therapeutics, announced top-line results from the second Phase III study (RX-3341-303, NCT01984684) of Baxdela (delafloxacin), an investigational anionic quinolone in development for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Baxdela met the primary endpoints required by the FDA as well as the European Medicines Agency (EMA) in this confirmatory pivotal study. Baxdela, with its broad spectrum activity against Gram-positive and Gram-negative bacteria, including MRSA, was tested as an intravenous (IV)-to-oral monotherapy against standard of care, IV-only combination of vancomycin plus aztreonam.

In the intent-to-treat population (ITT), IV-to-oral Baxdela met the FDA’s primary endpoint of statistical non-inferiority (10% non-inferiority margin) at the early clinical response at 48-72 hours after initiation of therapy (83.7%) compared to IV vancomycin combination therapy with aztreonam (80.6%). The 95% confidence interval for the treatment difference had lower and upper bounds of -2.0% and 8.3%, respectively. Baxdela also met the EMA’s required endpoint of statistical non-inferiority (57.7%) compared to vancomycin plus aztreonam (59.7%) based on the investigator’s assessment of complete cure (resolution of all baseline signs and symptoms) at the follow-up visit in the ITT population. Lower and upper bounds of the 95% confidence interval for the treatment difference were -8.6% and 4.6%, respectively. In addition, Baxdela was comparable to vancomycin plus aztreonam in achieving treatment success at Follow-Up (cure or improved, with no further antibiotics needed) with success rate of 87.2% vs 84.8%, respectively. IV/oral Baxdela monotherapy successfully eradicated Gram-positive pathogens, including MRSA, and Gram-negative pathogens at rates comparable to IV vancomycin/aztreonam combination treatment. Both intravenous (IV) and oral Baxdela were well tolerated in the study participants. Overall adverse event rates were similar between treatment arms.

The most common treatment-emergent adverse events on Baxdela were diarrhea and nausea, which were generally mild and did not lead to treatment discontinuation. The oral formulation of Baxdela was well tolerated with no increase in GI events compared to the IV formulation. Only 1.2% of Baxdela-treated patients discontinued due to treatment-related adverse events. In this study, obese patients (BMI? 30kg/m2) constituted 50% of the enrolled population and had a higher prevalence of co-morbidities such as diabetes and cardiovascular disease than non-obese patients. Co-morbidities present challenges to appropriate antibiotic selection due to factors such as pathogen coverage, underlying disease, concomitant medications, drug metabolism and other issues.

Comment: Melinta Therapeutics states that it is on track to file for an approval of Baxdela later this year .