Zai Lab + Entasis Therapeutics announce positive topline results for sulbactam-durlobactam (SUL-DUR)

SUL-DUR met the primary endpoint of 28-day all-cause mortality in patients with carbapenem-resistant Acinetobacter infections (CRABC m-MITT population in Part A of the study), demonstrating statistical non-inferiority versus colistin. Mortality analyses favored SUL-DUR versus colistin in CRABC m-MITT and all study populations included in the topline results. At Test of Cure, there was a statistically significant difference in clinical response favoring SUL-DUR over colistin. SUL-DUR met the primary safety objective of the study achieving statistically significant reduction in nephrotoxicity.

ATTACK; enrolled 207 patients at 95 clinical sites in 17 countries. This was a two-part trial with Part A being the randomized, comparative portion (SUL-DUR versus colistin) in patients with documented Acinetobacter baumannii hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), ventilated pneumonia (VP), or bacteremia and Part B being an open-labeled portion (SUL-DUR only) including ABC infections resistant to or failed colistin or polymyxin B treatment. All patients received imipenem/cilastatin as background therapy. Approximately 95% of baseline Acinetobacter isolates tested were carbapenem resistant.

SUL-DUR met the primary efficacy endpoint of 28-day all-cause mortality compared to colistin in the CRABC m-MITT (carbapenem-resistant Acinetobacter infections ) population (n=125) of Part A. SUL-DUR mortality was 19.0% (12/63) compared to 32.3% (20/62) in the colistin arm (treatment difference of -13.2%; 95% CI: -30.0, 3.5). Similar trends were observed in 28-day and 14-day all-cause mortality favoring SUL-DUR across all study populations evaluated to date A statistically significant difference in clinical cure at Test of Cure (TOC) was observed with 61.9% in SUL-DUR arm compared to 40.3% in the colistin arm (95% CI: 2.9, 40.3).In Part B, the 28-day all-cause mortality was 17.9% (5/28) and consistent with that observed in Part A. Safety analyses were conducted in a total of 205 patients with at least one dose in Part A and Part B.

SUL-DUR met the primary safety objective with a statistically significant reduction in nephrotoxicity as measured by the RIFLE classification. SUL-DUR nephrotoxicity was 13.2% (12/91) versus 37.6% (32/85) in the colistin arm (p = 0. 0002). Overall adverse events (AEs) in the safety population were comparable between treatment groups with 87.9% (80/91) in the SUL-DUR arm versus 94.2% (81/86) in the colistin arm in Part A, 89.3% (25/28) in Part B. Drug related AEs were 12.1% (11/91) with SUL-DUR compared to 30.2% (26/86) with colistin in Part A, 10.7% (3/28) in Part B.