FDA Accepts Application for Antibiotic for Drug-Resistant Infections

The FDA has accepted for priority review Innoviva’s new drug application (NDA) for SUL-DUR to treat patients with infections caused by Acinetobacter baumannii-calcoaceticus complex (ABC). The agency is planning to hold an advisory committee meeting to discuss this application. The target PDUFA date is May 29, 2023.

Acinetobacter baumannii-calcoaceticus complex results in severe pneumonia and bloodstream infections, as well as infections of the urinary tract and the skin. ABC is considered a global threat in the healthcare setting due in part to its ability to acquire multidrug resistance.

Carbapenem-resistant Acinetobacter infections are among the top antibiotic-resistant threats, according to the Centers for Disease Control and Prevention. Those at risk include hospital-based patients who are on ventilators, have devices such as catheters, have open wounds and are in intensive care units. An estimated 8,500 infections in hospitalized patients and 700 estimated deaths in the United States are caused by carbapenem-resistant Acinetobacter, according to the CDC.

Sulbactam-durlobactam (SUL-DUR) is an intravenous drug that is a combination of sulbactam, an IV β-lactam antibiotic, and durlobactam, a broad-spectrum IV β-lactamase inhibitor, being developed to treat infections caused by ABC, including multi-drug and carbapenem-resistant strains.

David Altarac, M.D.

“Carbapenem-resistant and multidrug-resistant Acinetobacter infections are an urgent and emergent threat due to increasing rates of resistance and few viable treatment options,” David Altarac, M.D., chief medical officer of Entasis Therapeutics, a subsidiary of Innoviva, said in a press release. SUL-DUR was developed by Entasis, which was acquired by Innoviva in July 2022.

The application is based on the phase 3 ATTACK trial. In the trial, SUL-DUR demonstrated statistical non-inferiority versus colistin, a last-resort antibiotic for drug resistant pathogens, for the primary endpoint of 28-day all-cause mortality in patients with carbapenem-resistant ABC infections and a significant difference in clinical cure rates. In part A of the study, clinical cure rates were 61.9% for SUL-DUR and 40.3% versus colistin.

SUL-DUR also exhibited a favorable safety profile with statistically significant reduction in nephrotoxicity, 13.2% for SUR-DUR versus 37.6% for colistin.