In a development that could offer new hope for multidrug-resistant infections, US pharmaceutical giant Pfizer has recently announced that its investigational antibiotic combination aztreonam-avibactam has shown positive results in treating serious bacterial infections due to Gram-negative bacteria, including Metallo-β-lactamase (MBL)-producing multidrug-resistant pathogens for which there are limited or no treatment options.
The drug major said in a statement that the Phase 3 programme, which included the REVISIT (NCT03329092) and ASSEMBLE (NCT03580044) studies evaluating the efficacy, safety, and tolerability of the novel investigational antibiotic combination, discovered that the drug is effective and well-tolerated, with no new safety findings and a safety profile similar to aztreonam alone.
Commenting on the trial results, James Rusnak, Senior Vice President and Chief Development Officer, Internal Medicine, Anti-Infectives and Hospital at Pfizer, said, “We believe these data demonstrate that ATM-AVI if approved, could be an important treatment option for patients with life-threatening bacterial infections that are resistant to almost all currently available antibiotics.”
“We are committed to meeting this critical need and helping to address the global health threat of antimicrobial resistance,” he added.
The REVISIT study compared ATM-AVI metronidazole (MTZ) to meropenem (MER) colistin (COL) for the treatment of complicated intra-abdominal infections, hospital-acquired pneumonia, and ventilator-associated pneumonia, and discovered that all-cause mortality on day 28 was nearly half (10.8%) in the ATM-AVI MTZ group compared to 19.4% in the MER COL group.
The ASSEMBLE trial indicated that 5/12 (41.7%) of ATM-AVI MTZ patients with infections caused by verified MBL-producing Gram-negative bacteria were healed at TOC, compared to 0/3 (0%) of those on best available therapy (BAT). ATM-AVI patients experienced TEAEs that were in line with those of aztreonam alone. No patient treated with ATM-AVI experienced a treatment-related SAE.
“These clinical findings show that ATM-AVI, if approved, could help provide coverage against Gram-negative bacteria without compromising on efficacy or safety,” said Yehuda Carmeli, Head of the National Institute for Antibiotic Resistance and Infection Control, Tel Aviv Medical Center, Israel.
“These data are particularly promising, given the complexities of managing cIAI and HAP/VAP infections in these hospitalised, critically ill patients, and the challenges of real-world patient recruitment within this population,” he added.
Pfizer informed us that it expects to submit the full results of the studies for scientific publication.
It further informed that these data are expected to form the basis for planned regulatory filings in the European Union, United Kingdom, China, and the U.S. in the second half of 2023.