The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for sulbactam-durlobactam for the treatment of infections caused by Acinetobacter baumannii-calcoaceticus complex (ABC), including multidrug resistant and carbapenem-resistant strains.
The investigational intravenous product is a combination of sulbactam, a β-lactam antibiotic, and durlobactam, a broad-spectrum β-lactamase inhibitor. The NDA submission includes data from the phase 3 ATTACK trial (ClinicalTrials.gov Identifier: NCT03894046), which evaluated sulbactam-durlobactam vs colistin in patients with documented Acinetobacter baumannii hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bacteremia (Part A of the study).
Sulbactam-durlobactam was found to be statistically noninferior to colistin for the primary endpoint of 28-day all-cause mortality in patients with carbapenem-resistant Acinetobacter infections. The mortality rate was 19.0% (12/63) in the sulbactam-durlobactam arm and 32.3% (20/62) in the colistin arm (treatment difference, 13.2%; 95% CI, -30.0, 3.5). Additionally, a statistically significant difference in clinical cure rates was observed (61.9% with sulbactam-durlobactam vs 40.3% with colistin).
In the open-label portion of the study (Part B), 28-day all-cause mortality among patients with ABC infections who did not tolerate colistin/polymyxin B or whose pathogens were resistant to colistin/polymyxin B was reported to be 17.9% (5/28).
As for safety, a statistically significant reduction in nephrotoxicity (the primary safety objective) was observed in patients treated with sulbactam-durlobactam vs those who received colistin (13.2% vs 37.6%, respectively; P =.0002).
“Carbapenem-resistant and multidrug-resistant Acinetobacter infections are an urgent and emergent threat due to increasing rates of resistance and few viable treatment options,” said David Altarac, MD, Chief Medical Officer of Entasis Therapeutics. “The acceptance of our NDA brings us one step closer to potentially delivering [sulbactam-durlobactam] to patients in this area of high unmet medical need.”
A Prescription Drug User Fee Act target date of May 29, 2023 has been assigned to the application.
- Innoviva announces FDA acceptance and Priority Review of New Drug Application for sulbactam-durlobactam (SUL-DUR). News release. December 1, 2022. https://www.businesswire.com/news/home/20221130006085/en/Innoviva-Announces-FDA-Acceptance-and-Priority-Review-of-New-Drug-Application-for-Sulbactam-Durlobactam-SUL-DUR.
- Entasis Therapeutics announces positive topline results for sulbactam-durlobactam (SUL-DUR) from the phase 3 ATTACK trial. News release. October 18, 2021. https://investors.entasistx.com/news-releases/news-release-details/entasis-therapeutics-announces-positive-topline-results.