FDA committee unanimously recommends pneumonia antibiotic for adults
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Key takeaways:
- The 28-day all-cause mortality for patients given sulbactam-durlobactam was 19%.
- Fewer treatment-emergent adverse events were reported among patients given sulbactam-durlobactam vs. colistin.
The FDA’s Antimicrobial Drugs Advisory Committee voted unanimously in favor of approving sulbactam-durlobactam for adults with hospital-acquired and ventilator-associated bacterial pneumonia, Innoviva announced Monday.
According to Innoviva, the FDA committee specifically supported the approval of sulbactam-durlobactam for the treatment of adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex.
Carbapenem-resistant Acinetobacter baumannii, a CDC-designated urgent public health threat, was among the top six leading pathogens for deaths associated with resistance in 2019 and was designated a priority pathogen by WHO, according to data shared by Innoviva. The company added that infections caused by drug-resistant Acinetobacter are serious and life-threatening conditions with high morbidity and mortality, highlighting the importance of treatment options.
The FDA committee based its recommendation on positive results from a two-part phase 3 trial assessing the safety and efficacy of sulbactam-durlobactam vs. colistin in patients with infections caused by Acinetobacter.
The first part of the study was a randomized, assessor-blinded, comparative study, during which adult patients were randomly assigned 1:1 to receive 1 g sulbactam/1 g durlobactam or 2.5 mg/kg colistin.
The second part of the study was an open-label study including adult patients known to have hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia and/or bacteremia infections associated with Acinetobacter baumannii-calcoaceticus (ABC) organisms resistant to colistin or polymyxin B.
The results showed that in the first part of the study, the 28-day all-cause mortality for the sulbactam-durlobactam group was 19% and was 32.3% in the colistin group with a treatment difference of 13.2% (95% CI, 30% to 3.5%).
Additionally, there was a significant difference of 21.6% (95% CI, 2.9%-40.3%) in the clinical cure rate at time of cure (TOC), with 61.9% of patients in sulbactam-durlobactam group vs. 40.3% in the colistin group.
In the second part of the study, the researchers found that patients who were intolerant to colistin or had infections caused by colistin-resistant ABC were similar to patients given sulbactam-durlobactam in the first part of the study, with the overall, 28-day all-cause mortality being 17.9% (95%, CI 6.1%-36.%) for the intention to treat population. Clinical cure at TOC was seen in 71.4% of patients.
Additional data derived from the study showed that sulbactam-durlobactam was also deemed safe and had a lower overall incidence of treatment-emergent adverse events (87.4% of sulbactam-durlobactam patients — 42.9% in part one of the study, 32.1% in part two — vs. 94.2% in the colistin group).
"The committee’s unanimous recommendation in favor of sulbactam-durlobactam, the first pathogen-targeted therapy for Acinetobacter, moves us closer to potentially addressing the urgent need for new treatment options for patients with serious and life-threatening infections caused by this pathogen,” David Altarac, MD, chief medical officer of Entasis Therapeutics, said in a press release. “We appreciate the committee’s thoughtful deliberation and strong vote of confidence and look forward to working with the FDA as it completes its review.”
A Prescription Drug User Fee Act target action date has been set for May 29.
References:
- FDA. UPDATED INFORMATION: April 17, 2023: Meeting of the Antimicrobial Drugs Advisory Committee Meeting Announcement. https://www.fda.gov/advisory-committees/advisory-committee-calendar/updated-information-april-17-2023-meeting-antimicrobial-drugs-advisory-committee-meeting. Updated April 17, 2023. Accessed April 18, 2023.
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