Alita Miller, PhD, senior vice president of research at Entasis Therapeutics, discusses positive trial data for Sulbactam-durlobactam (SUL-DUR) slated to be presented at ECCMID 2023.
“We’re looking to find novel ways to treat resistant infections that have very high unmet medical needs,” said Alita Miller, PhD, senior vice president of research at Entasis Therapeutics.
Miller met with Contagion to discuss research slated to be presented at the 2023 European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).
Sulbactam-durlobactam (SUL-DUR) is an intravenous investigational therapy that is a combination of sulbactam, an IV β-lactam antibiotic, and durlobactam, a novel broad-spectrum IV β-lactamase inhibitor. SUL-DUR targets Acinetobacter baumannii infections, including those caused by multidrug-resistant and carbapenem-resistant (CRAB) strains.
“Acinetobacter is recognized by the WHO and the CDC as a very high unmet medical need,” Miller said. “It’s actually the fifth leading cause of death across the world that’s attributed to drug resistance in nonbacteria.”
The high drug resistance of Acinetobacter means that there are not many treatment options, and Miller noted there is no clear standard of care for these infections.
One poster presentation examined the efficacy of sulbactam-durlobactam versus colistin for the treatment of infections caused by Acinetobacter baumannii-calcoaceticus complex (ABC). Miller and fellow investigators chose colistin as the comparator because it is known to have very low rates of resistance, about 4% worldwide.
However, in phase 3 trials, Miller said colistin resistance was found to be up to 17%. “The poster at ECCMID describes 3 different colistin-resistant outbreaks” Miller explained. “What we were pleased to see is the patients who had those colistin-resistant infections were effectively treated by sulbactam-durlobactam. The majority of them survived to 28 days and had favorable clinical and microbiological outcomes.”
The primary efficacy endpoints for this study were all-cause mortality at 28 days and reduction in nephrotoxicity; sulbactam-durlobactam performed better than colistin on both counts. SUL-DUR also met its secondary trial endpoints, including clinical cure and microbiological outcome.
Miller and her team submitted a new drug application (NDA) to the US Food and Drug Administration (FDA) and was granted an advisory committee meeting, scheduled for April 17. The PDUFA date for Entasis’s sulbactam-durlobactam is May 29, 2023, and the agent could be available soon after if approved.
“We feel the evidence is very robust to show that sulbactam-durlobactam represents a potential new therapeutic option for the treatment of these drug-resistant Acinetobacter infections,” said Miller. “For the first time, physicians will have something to treat these infections, which otherwise have very high rates of morbidity and mortality.”