Antibiotic Shows Noninferiority Vs Colistin for Acinetobacter infections


Sulbactam-durlobactam is efficacious against carbapenem-resistant infections, and Innoviva is preparing for the antibiotic's PDUFA at the end of this month.

Sulbactam-durlobactam demonstrated statistical non-inferiority versus colistin for the primary endpoint of 28-day all-cause mortality in patients with carbapenem-resistant Acinetobacter baumannii.

This investigational antibiotic is an intravenous, investigational drug that is a combination of sulbactam, a beta-lactam antibacterial, and durlobactam, a beta-lactamase inhibitor.

The study’s results were published in The Lancet Infectious Diseases.

What the Data Shows
The phase 3 trial evaluated the safety and efficacy of sulbactam-durlobactam versus colistin in patients with infections caused by Acinetobacter. In the trial, sulbactam-durlobactam demonstrated statistical non-inferiority versus colistin for the primary endpoint of 28-day all-cause mortality in patients with carbapenem-resistant Acinetobacter infections and a significant difference in clinical cure rates.

For the study, 181 patients were randomly assigned to either sulbactam–durlobactam or colistin. There were 176 hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, or ventilated pneumonia cases and 5 bloodstream infections.

Of these, 125 of the participants was confirmed with laboratory-confirmed carbapenem-resistant ABC isolates were included in the primary efficacy analysis. 28-day all-cause mortality was 12 (19%) of 63 in the sulbactam–durlobactam group and 20 (32%) of 62 in the colistin group, a difference of –13·2% (95% CI –30·0 to 3·5), which met criteria for non-inferiority.

“The safety and efficacy demonstrated during the phase 3 ATTACK trial by sulbactam-durlobactam, which was designed specifically for treating serious infections caused by Acinetobacter, are very promising, and provide hope that we’ll have a novel, desperately needed, effective treatment option against this lethal pathogen,” said Keith Kaye, MD, MPH, chief, Division of Allergy, Immunology and Infectious Diseases at Rutgers Robert Wood Johnson Medical School.

Sulbactam-durlobactam also exhibited a favorable safety profile with a statistically significant lower incidence of nephrotoxicity as measured by modified Risk–Injury–Failure–Loss and End-stage kidney disease (RIFLE) criteria. "Incidence of nephrotoxicity was significantly (p<0·001) lower with sulbactam–durlobactam than colistin (12 [13%] of 91 vs 32 [38%] of 85),” the investigators wrote.

Serious adverse events were reported in 36 (40%) of 91 patients in the sulbactam–durlobactam group and 42 (49%) of 86 patients in the colistin group. Treatment-related adverse events leading to study drug discontinuation were reported in ten (11%) of 91 patients in the sulbactam–durlobactam group and 14 (16%) of 86 patients in the colistin group.”

Innoviva Launches Subsidiary
Sulbactam-durlobactam was developed by Entasis Therapeutics, which was acquired by Innoviva last year. Earlier this week, Innoviva introduced Innoviva Specialty Therapeutics, which is a subsidiary focused on developing therapies on critical care and infectious disease. The new subsidiary integrates Entasis and La Jolla Pharmaceutical company. Innoviva completed the acquisition of La Jolla last year as well.

“We see significant unmet need and are confident we can benefit seriously ill patients and create shareholder value by delivering differentiated, novel therapies in critical care and infectious disease,” Innoviva CEO Pavel Raifeld, said in a statement. “Rooted in the strengths of Entasis and La Jolla, Innoviva Specialty Therapeutics is an integrated business with excellent capabilities and significant expertise in these settings that enable us to focus on the unique challenges and needs of all stakeholders.”

FDA Committee Weighs in, Next Steps
Last month, the FDA’s Antimicrobial Drugs Advisory Committee (AMDAC) voted 12-0 in favor of recommending FDA approval for sulbactam-durlobactam for the indication of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii.

Next up for the therapy is its PDUFA action date, which is May 29.

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