Positive results have been reported from a phase 3, randomized, double-blind study of delafloxacin (Baxdela, Melinta Therapeutics), an investigational anionic quinolone in development for the treatment of patients with acute bacterial skin and skin-structure infections (ABSSSIs). Intravenous (IV)-to-oral monotherapy with delafloxacin was compared with the standard-of-care, IV-only combination of vancomycin and aztreonam. Delafloxacin met the primary endpoints required by the FDA in this pivotal trial.
In the delafloxacin arm, patients received 300 mg of IV delafloxacin every 12 hours for six doses, followed by 450 mg of oral delafloxacin every 12 hours. The comparator treatment consisted of IV vancomycin 15 mg/kg every 12 hours, based on actual body weight, plus 1 to 2 g of IV aztreonam every 12 hours. The duration of treatment in either arm was five to 14 days, based on the physician’s judgment. All of the patients were asked to return for a follow-up visit on day 14 ± 1 and for a late follow-up visit on days 21 to 28.
In the intent-to-treat (ITT) population, IV-to-oral delafloxacin achieved the primary endpoint of statistical noninferiority in the early clinical response at 48 to 72 hours after initiation of therapy (83.7%) compared with IV combination therapy with vancomycin and aztreonam (80.6%). Delafloxacin also met the endpoint of statistical noninferiority (57.7%) compared with vancomycin plus aztreonam (59.7%) based on the investigators’ assessment of a complete cure (i.e., the resolution of all baseline signs and symptoms) at the follow-up visit in the ITT population.
Further, delafloxacin was comparable with vancomycin plus aztreonam in achieving treatment success at follow-up (i.e., cured or improved, with no further antibiotics needed), with a success rate of 87.2% versus 84.8%, respectively. IV/oral delafloxacin monotherapy successfully eradicated gram-positive pathogens (including methicillin-resistant Staphylococcus aureus [MRSA]) and gram-negative pathogens at rates comparable with those of IV combination treatment with vancomycin/aztreonam.
The most common treatment-emergent adverse events associated with delafloxacin were diarrhea and nausea, which were generally mild and did not lead to treatment discontinuation. The oral formulation of delafloxacin was well tolerated, with no increase in gastrointestinal events compared with the IV formulation. In the delafloxacin group, 1.2% of patients discontinued treatment because of treatment-related adverse events.
Serious skin infections, including wounds, abscesses, and cellulitis, disproportionately affect patients with underlying diseases, such as obesity, diabetes, and cardiovascular conditions. While many of these infections are caused by gram-positive pathogens, including MRSA, a significant percentage are gram-negative or mixed. In most cases, a pathogen is not identified, requiring empiric therapy.
Source: Melinta Therapeutics; May 12, 2016.