The Food and Drug Administration (FDA) has approved Xacduro® (sulbactam for injection; durlobactam for injection) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex in patients 18 years of age and older.
Xacduro is a co-packaged product containing sulbactam, a beta-lactam antibacterial and beta lactamase inhibitor, and durlobactam, a beta lactamase inhibitor. The approval was based data from the phase 3 ATTACK trial (ClinicalTrials.gov Identifier: NCT03894046), which evaluated Xacduro vs colistin in patients with documented A baumannii hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bacteremia; the majority of patients had pneumonia as the baseline infection.
Xacduro 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 Xacduro 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 Xacduro vs 40.3% with colistin. Clinical cure was defined as complete resolution or significant improvement of signs and symptoms that were present at baseline and no new symptoms, such that no additional gram-negative antimicrobial therapy was warranted.
As for safety, a statistically significant reduction in nephrotoxicity (the primary safety objective) was observed in patients treated with Xacduro vs those who received colistin (13% vs 38%, respectively; P =.0002). The most common adverse reactions reported were liver test abnormalities, diarrhea, anemia, and hypokalemia.
“Acinetobacter poses a significant danger to hospitalized patients, who are generally very ill and particularly susceptible to infections,” said Andrew F. Shorr, MD, MPH, MBA, Clinical Professor of Medicine, Georgetown University School of Medicine, Washington, DC and an investigator on the ATTACK trial. “Effectively treating infections caused by drug-resistant Acinetobacter is a challenge and makes this patient population in high need of new, effective treatment options. I’m encouraged by the approval of co-packaged sulbactam-durlobactam as it means physicians will soon have a novel therapeutic option that may help to address this urgent public health threat.”
Xacduro is supplied as a kit containing a single dose vial of sulbactam 1g and 2 single-dose vials of durlobactam (0.5g in each vial). The product requires reconstitution and further dilution prior to intravenous infusion. The recommended duration of treatment is 7 to 14 days; the duration of therapy is guided by the patient’s clinical status. The dosing regimen should be adjusted based on renal function.
Xacduro is expected to be available later this year.
This article originally appeared on MPR
- Innoviva Specialty Therapeutics announces FDA approval for Xacduro® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use. News release. May 23, 2023. https://www.businesswire.com/news/home/20230523005961/en/Innoviva-Specialty-Therapeutics-Announces-FDA-Approval-for-XACDURO%C2%AE-sulbactam-for-injection-durlobactam-for-injection-Co-packaged-for-Intravenous-Use.
- Kaye KS, Shorr AF, Wunderink RG, et al. Efficacy and safety of sulbactam–durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii–calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK). The Lancet Infectious Diseases. Published online May 11, 2023. doi:10.1016/S1473-3099(23)00184-6
- Xacduro. Package insert. Innoviva; 2023. Accessed May 24, 2023. https://innovivaspecialtytherapeutics.com/wp-content/uploads/2023/05/Xacduro_Full_Prescribing_Information.pdf.