Pfizer Inc. (NYSE: PFE) announced positive results from the Phase 3 program comprising the REVISIT (NCT03329092) and ASSEMBLE (NCT03580044) studies evaluating the efficacy, safety, and tolerability of the novel investigational antibiotic combination aztreonam-avibactam (ATM-AVI) 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.
Data support that ATM-AVI is effective and well-tolerated, with no new safety findings and a similar safety profile to aztreonam alone. “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,” said James Rusnak, Senior Vice President and Chief Development Officer, Internal Medicine, Anti-Infectives and Hospital, Pfizer. “We are committed to meeting this critical need and helping to address the global health threat of antimicrobial resistance.”
The REVISIT study compared ATM-AVI ± metronidazole (MTZ) with meropenem (MER) ± colistin (COL)for the treatment of complicated intra-abdominal infections (cIAI), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP).
Threat to global health
Antimicrobial resistance (AMR), particularly in Gram-negative bacteria, is widely recognized as one of the biggest threats to global health and developing new treatments for infections caused by these bacteria has been highlighted as a critical area of need by the World Health Organization (WHO).1 An estimated 1.27 million deaths globally were caused by bacterial AMR in 2019 alone.2 Without solutions, a continued rise of AMR could make routine medical procedures too risky to perform.3
“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, National Institute for Antibiotic Resistance and Infection Control, Tel Aviv Medical Center, Tel Aviv, Israel. “These data are particularly promising given the complexities of managing cIAI and HAP/VAP infections in these hospitalized, critically ill patients, and the challenges of real-world patient recruitment within this population.”
Full results from the studies will be submitted for scientific publication. Data from the REVISIT and ASSEMBLE studies 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. Pfizer holds the global rights to commercialize ATM-AVI outside of the U.S. and Canada, where the rights are held by its development partner AbbVie.
About Aztreonam-Avibactam (ATM-AVI)
Aztreonam-avibactam (ATM-AVI) is an investigational treatment for infections caused by Gram-negative bacteria with limited treatment options.4,5,6 It combines aztreonam, a monobactam β-lactam, with avibactam, a recent broad-spectrum β-lactamase inhibitor.5,6
Metallo-β-lactamases (MBLs) are a class of β-lactamase enzymes which are not inhibited by current β-lactamase inhibitors and hydrolyze nearly all β-lactam antibiotics, the exception being monobactams such as aztreonam. However, monobactams are degraded by other β-lactamases that are frequently co-produced with MBLs, limiting the clinical usefulness of aztreonam monotherapy.
The combination of aztreonam with avibactam restores aztreonam’s activity against bacteria that co-produce MBLs and other β-lactamases and, if approved, could offer a much-needed safe and effective treatment option against multidrug-resistant Gram-negative bacteria.5
For more information and key results, visit Pfizer.
References
1 Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318-327.
2 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629-655.
3 World Health Organization. Antibiotic resistance factsheet. July 2020. Available at: https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance Last accessed May 2023.
4 Sader et al. Aztreonam/avibactam activity against clinical isolates of Enterobacterales collected in Europe, Asia and Latin America in 2019. J Antimicrob Chemother. 2021;76:659-666.
5 Rossolini et al.In vitro activity of aztreonam/avibactam against isolates of Enterobacterales collected globally from ATLAS in 2019. J Global Antimicrob Resist.2022;30:214-221
6 Cornely OA, Cisneros JM, Torre-Cisneros J, et al. Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study. J Antimicrob Chemother 2020;75:618–27.