Sulbactam-Durlobactam (SUL-DUR) Effectively Treats Carbapenem-Resistant Acinetobacter Baumannii
In a phase 3 trial, sulbactam-durlobactam (SUL-DUR) was found to more favorably treat carbapenem-resistant Acinetobacter baumannii (CRAB) than colistin.
Sulbactam-durlobactam (SUL-DUR) is the first drug to achieve statistical non-inferiority in 28-day all-cause mortality in carbapenem-resistant Acinetobacter baumannii (CRAB) patients.
SUL-DUR was developed by Entasis Therapeutics Holdings Inc. for patients with multidrug-resistant Gram-negative infections caused by CRAB.
Its global phase 3 registrational ATTACK trial, executed at Zai Lab, evaluated the safety and efficacy of SUL-DUR versus colistin in patients with CRAB infection.
“ATTACK was a landmark clinical trial, the first to successfully evaluate an investigational agent targeting a specific drug-resistant Gram-negative pathogen. SUL-DUR is the first investigational drug to demonstrate efficacy in a 28-day all-cause mortality trial focused on carbapenem-resistant Acinetobacter, an ‘Urgent’ threat as designated by the CDC,” said Manos Perros, CEO at Entasis.
The trial enrolled 207 CRAB patients at 95 clinical sites across 17 countries. The first part of the trial was randomized and compared SUL-DUR to colistin in patients with documented Acinetobacter baumannii hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), ventilated pneumonia (VP), or bacteremia. SUL-DUR mortality was 19.0% (12/63) compared to 32.3% (20/62) in the colistin arm.
Part B of the study was open-label and only included SUL-DUR. It measured efficacy of SUL-DUR against ABC infections resistant to colistin or polymyxin B treatment. All patients received imipenem/cilastatin as background therapy, and an estimated 95% of tested baseline Acinetobacter isolates were carbapenem resistant. At the close of Part B, the 28-day all-cause mortality was 17.9% (5/28), consistent with Part A.
A statistically significant difference in clinical response at Test of Cure favored SUL-DUR over colistin, with 61.9% in the SUL-DUR arm and 40.3% in the colistin arm. The primary objective of the study was to significantly reduce nephrotoxicity, which SUL-DUR achieved.
According to Dr. Samantha Du, Chairperson and CEO at Zai Lab, “CRAB infections are among the worst bacterial infections, and safe and effective treatment options are limited. We look forward to bringing this drug to China, where CRAB infections are still frequently seen in ICUs and result in high morbidity and mortality.”
Entasis Therapeutics plans to submit SUL-DUR for a New Drug Application (NDA) in mid-2022.
Entasis Therapeutics Holdings Inc. is a clinical-stage biopharmaceutical company that specializes in novel antibacterial products. They specialize in discovering and developing treatments for multidrug-resistant Gram-negative bacteria, like CRAB.