What a Newly FDA Approved Antibiotic Means to Clinicians, Patients

Late yesterday, the FDA approved Innoviva’s antibiotic, sulbactam-durlobactam (Xacduro) for treatment of patients 18 years of age and older with hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) caused by susceptible strains of the pathogen, Acinetobacter baumannii.

To give a sense of how this therapy is being received already, Contagion Editor-in-Chief Jason Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS, encapsulated the feeling of clinicians when he tweeted: “I really hope this drug is successful. It is tailor-made for one highly resistant organism—the exact kind of antibiotic that clinicians say they want, but are commercially challenging.”

This really underscores the need for clinicians to have new antibiotics.

This multidrug resistant bacterial strain, Acinetobacter baumannii, is particularly challenging, Keith Kaye, MD, MPH, chief, Division of Allergy, Immunology and Infectious Diseases at Rutgers Robert Wood Johnson Medical School explained. “Acinetobacter baumannii in certain parts of the country and certain parts of the world is really a hyperendemic, major problem,” Kaye said. “The resistance problems we are seeing in Acinetobacter baumannii and the lack of effective treatment options really has equaled sort of an infectious disease emergency for vulnerable hospital patients.”

The good news is the company’s manufacturer, Innoviva Specialty Therapeutics, anticipates the antibiotic will be available later this year.

Data from the antibiotic's pivotal phase 3 ATTACK trial were recently published in The Lancet Infectious Diseases. Sulbactam-durlobactam demonstrated statistical non-inferiority versus colistin for the primary end point of 28-day all-cause mortality in patients with carbapenem-resistant Acinetobacter baumannii and demonstrated a significant difference in clinical cure rates.

For the study, 181 patients were randomly assigned to either sulbactam–durlobactam or colistin. There were 176 hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, or ventilated pneumonia cases and 5 bloodstream infections.

Of these, 125 of the participants was confirmed with laboratory-confirmed carbapenem-resistant ABC isolates were included in the primary efficacy analysis. 28-day all-cause mortality was 12 (19%) of 63 in the sulbactam–durlobactam group and 20 (32%) of 62 in the colistin group, a difference of –13·2% (95% CI –30·0 to 3·5), which met criteria for non-inferiority.

The antibiotic is co-packaged for intravenous use as a combination of sulbactam, a beta-lactam antibacterial, and durlobactam, a beta-lactamase inhibitor.

The new drug application was filed by Entasis Therapeutics Inc, an affiliate of Innoviva Specialty Therapeutics. Xacduro was granted Priority Review and designated as a Qualified Infectious Disease Product.

Contagion spoke to Kaye this week just prior to the FDA approval about the study’s results and why this antibiotic is so important to clinicians and patients.