The US Food and Drug Administration (FDA) approved Innoviva Specialty Therapeutics’ Xacduro (sulbactam for injection; durlobactam for injection)—a new treatment for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible strains of bacteria called Acinetobacter baumannii-calcoaceticus complex—for intravenous use in patients 18 years of age and older.

Acinetobacter species top the list of critical bacterial pathogens that pose the greatest threat to human health, highlighting the high level of need for additional treatment options amid growing global resistance to antimicrobial medicines, according to the World Health Organization.

“Xacduro is the first pathogen-targeted therapy approved to treat hospital-acquired and ventilator-associated pneumonias caused by Acinetobacter. The FDA approval of Xacduro marks an important milestone in our aim to deliver differentiated therapies to critically ill patients who have limited treatment options,” says David Altarac, MD, chief medical officer at Innoviva Specialty Therapeutics, in a release. “Drug-resistant Acinetobacter can cause serious and even life-threatening infections that are associated with high morbidity and mortality, and long, expensive hospital stays, as the pathogen continues to acquire resistance genes for almost all antibiotics used to treat Gram-negative bacteria.”

Acinetobacter baumannii-calcoaceticus complex (henceforth referred to as A. baumannii) includes four species of bacteria in the Acinetobacter family. These bacteria can cause infections in various parts of the body, occurring most frequently in healthcare settings and predominantly causing pneumonia. A. baumannii can become highly resistant to multiple antibacterial drugs and current treatment options for drug-resistant A. baumannii are limited. 

Xacduro consists of sulbactam, a drug structurally related to penicillin, and durlobactam. Sulbactam kills A. baumannii whereas durlobactam protects sulbactam from being degraded by enzymes that may be produced by A. baumannii. Xacduro is administered by intravenous infusion.

Xacduro’s efficacy was established in a multicenter, active-controlled, open-label (investigator-unblinded, assessor-blinded), non-inferiority clinical trial in 177 hospitalized adults with pneumonia caused by carbapenem-resistant A. baumannii. Patients received either Xacduro or colistin (a comparator antibiotic) for up to 14 days. Both treatment arms also received an additional antibiotic, imipenem/cilastatin, as background therapy for potential hospital-acquired/ventilator-associated bacterial pneumonia pathogens other than Acinetobacter baumannii-calcoaceticus complex. 

The primary measure of efficacy was mortality from all causes within 28 days of treatment in patients with a confirmed infection with carbapenem-resistant A. baumannii. Of those who received Xacduro, 19% (12 of 63 patients) died, compared to 32% (20 of 62 patients) who received colistin; this demonstrated that Xacduro was noninferior to colistin.

“Acinetobacter poses a significant danger to hospitalized patients, who are generally very ill and particularly susceptible to infections. Effectively treating infections caused by drug-resistant Acinetobacter is a challenge and makes this patient population in high need of new, effective treatment options,” says Andrew F. Shorr, MD, MPH, MBA, clinical professor of medicine at Georgetown University School of Medicine, in a release. “I’m encouraged by the approval of co-packaged sulbactam-durlobactam as it means physicians will soon have a novel therapeutic option that may help to address this urgent public health threat.”

The FDA granted Xacduro Fast Track, Qualified Infectious Disease Product, and Priority Review designations for this application.

“The FDA is dedicated to supporting the development of safe and effective treatment options for infections caused by difficult-to-treat bacteria like Acinetobacter baumannii-calcoaceticus complex,” says Peter Kim, MD, MS, director of the Division of Anti-Infectives in the FDA’s Center for Drug Evaluation and Research, in a release. “Today’s approval helps address a high unmet medical need by providing an additional treatment option for some of the sickest patients in our nation’s hospitals.”

Photo credit: Innoviva Specialty Therapeutics