Novel Antibiotics for Resistant Pathogens: Results of ATTACK Trial for Sulbactam-Durlobactam

Today, Entasis Therapeutics gave 2 presentations with promising results from their phase 3 ATTACK trial for Sulbactam-durlobactam (SUL-DUR). The data were presented today, April 26, on the last day of the 32nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), held in Lisbon, Portugal.

The first presentation, “Characterization of Acinetobacter baumannii-calcoaceticus complex (ABC) pathogens isolated at baseline from patients enrolled in the ATTACK Phase 3 trial,” was given by Alita Miller, PhD, the vice president of microbiology as Entasis. It reviewed the in vitro susceptibility of ABC isolates from 183 m-MITT patients enrolled in the ATTACK trial. The participants were in the ITT population and had received any study drug and had an ABC pathogen isolated at study baseline.

The pathogens harbored by the study participants were 96% carbapenem- and multidrug-resistant, 84% “extensively” drug-resistant, and 15% pan-drug resistant. The only comparator antibiotic was colistin, which demonstrated over 60% in vitro susceptibility.

Comparatively, only 4.6% of the isolates had SUL-DUR MICs >4 mg/L. Miller noted that susceptibility to SUL-DUR and comparators was consistent across infection types and geographic regions. The only excepting was colistin, with a non-susceptibility ranging from 0% in Latin America and China to 30% in Europe. Colistin non-susceptibility was also higher in isolates from bacteremic study patients.

The second oral presentation was given by David Altarac, MD, chief medical officer of Entasis: “Efficacy and safety of sulbactam-durlobactam (SUL-DUR) versus colistin therapy in patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections: A global, randomized, active-controlled Phase 3 trial (ATTACK).”

The ATTACK trial compared the safety and efficacy of SUL-DUR and colistin, in combination with imipenem/cilastatin, in patients with ABC infections. Part A of the trial was a randomized, blinded noninferiority study of SUL-DUR versus colistin in ABC hospital-acquired pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bacteremia, Part B was an open-label study of only SUL-DUR, including patients with ABC infections who either did not tolerate or had pathogens resistant to colistin/polymyxin B.

The primary efficacy endpoint of the ATTACK trial was 28-day all-cause mortality in the carbapenem resistant Acinetobacter baumannii-calcoaceticus (CRABC) m-MITT cohort. All-cause mortality in the cohort (n=125) was 19.0% for SUL-DUR and 32.3% for colistin. Clinical cure rates were 61.9% for SUL-DUR and 40.3% for colistin.

SUL-DUR previously became the first drug to achieve statistical non-inferiority in 28-day all-cause mortality in carbapenem-resistant Acinetobacter baumannii (CRAB) patients.

In addition to these 2 oral presentations, Entasis presented 5 posters expounding SUL-DUR and ATTACK results. Entasis Therapeutics is a late-stage clinical biopharmaceutical company that focuses on discovering, developing, and marketing antibacterial therapies that treat serious infections caused by multidrug-resistant Gram-negative bacteria.

These studies, “Characterization of Acinetobacter baumannii-calcoaceticus complex (ABC) pathogens isolated at baseline from patients enrolled in the ATTACK Phase 3 trial,” and “Efficacy and safety of sulbactam-durlobactam (SUL-DUR) versus colistin therapy in patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections: a global, randomized, active-controlled Phase 3 trial (ATTACK),” were presented at the 32nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), held April 23-26, 2022 in Lisbon, Portugal.