Baxdela well-tolerated, effective against ABSSSIs

NEW ORLEANS — Data from two phase 3 trials demonstrated that IV and oral Baxdela had similar safety and efficacy profiles against acute bacterial skin and skin structure infections, or ABSSSIs, compared with a combination regimen of vancomycin and aztreonam among patients with a history of infectious hepatitis.

Baxdela (delafloxacin, Melinta Therapeutics) is an investigational anionic fluoroquinolone that has activity against gram-negative and gram-positive organisms, including MRSA, according to Sue Cammarata, MD, chief medical officer of Melinta Therapeutics, and colleagues.

In two multicenter, double blind, phase 3 trials, researchers randomly assigned 1,510 patients in the United States, Europe, Latin America and Asia in a 1:1 ratio to receive either delafloxacin monotherapy or 15 mg/kg (actual body weight) of vancomycin plus aztreonam for 5 to 14 days. In one trial, patients in the delafloxacin arm received 300 mg IV twice daily. In the other trial, patients in the delafloxacin arm received 300 mg IV twice daily for 3 days and switched to an oral dose of 450 mg twice daily.

The cohort was diverse, according to Cammarata, and included elderly patients aged older than 65 years (14%) as well as those with obesity (42%), diabetes (11%), renal impairment (16.2%) and history of hepatitis (29%).

“These comorbidities all provide various challenges in antibiotic selection and dosing,” Cammarata told Infectious Disease News.

Of the 438 patients who had a history of hepatitis, the majority (92%) also had a history of substance abuse, which put them at an increased risk for MRSA, Cammarata said.

In the studies, for the patients with history of hepatitis, delafloxacin was noninferior to vancomycin/aztreonam at reducing lesion size at the primary infection site by at least 20% at 48 to 72 hours (86.4% vs. 86.7%). Delafloxacin also had comparable outcomes to vancomycin/aztreonam at a 14-day follow-up visit (83.2% vs. 83%) and a 21- to 28-day follow-up visit (80% vs. 80.3%), and had similar efficacy against MRSA (97.4% vs. 100%).

In a safety analysis, the percentage of patients with at least one treatment-emergent adverse event (AE) was lower in the delafloxacin arm compared with the vancomycin/aztreonam arm (49.5% vs. 60.4%). Aminotransferase increased in four patients who received delafloxacin and in six who received vancomycin/aztreonam. There were no discontinuations among patients who received delafloxacin due to treatment-related AEs. Three patients in the vancomycin/aztreonam arm discontinued treatment due to related AEs.

The researchers concluded that delafloxacin appeared to be safe and effective against ABSSSIs in a population with a history of infectious hepatitis and substance abuse.

“We believe that the ability to administer IV and oral Baxdela without the drug monitoring or weight-based dose-adjustments required by standard-of-care antibiotics like vancomycin will be appealing to many doctors,” Cammarata said. “The ability to switch patients from an IV to an oral antibiotic may also resonate with physicians, as it may facilitate hospital discharge, which could have meaningful economic implications.”

In October, Melinta Therapeutics submitted two New Drug Applications to the FDA for the approval of IV and oral Baxdela. The FDA previously designated delafloxacin as a Qualified Infectious Disease Product, expediting the review process. In addition, delafloxacin is being assessed for the treatment of urinary tract infections, and the FDA has granted the drug fast track designation for the treatment of community-acquired bacterial pneumonia. – by Stephanie Viguers

Reference:

Cammarata S, et al. Delafloxacin (DLX) is Effective and Well-Tolerated Compared to Vancomyin/Aztreonam (VAN/AZ) in Treatment of Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and History of Infectious Hepatitis. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Disclosure: Cammarata is an employee of Melinta Therapeutics.