European Commission Approves Pfizer’s Antibiotic Combination for Multidrug-Resistant Infections

With this approval, aztreonam-avibactam will be available in all 27 European Union (EU) member states, as well as in Iceland, Liechtenstein, and Norway.

Image credit: Pfizer

Yesterday, the European Commission granted marketing authorization for the combination antibiotic, aztreonam-avibactam (Emblaveo) for the treatment of adult patients with complicated intra-abdominal infections (cIAI), hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), and complicated urinary tract infections (cUTI), including pyelonephritis. In addition, the antibiotic is indicated for the treatment of infections due to aerobic gram-negative organisms in adult patients with limited treatment options.¹

With this approval, aztreonam-avibactam becomes the first β-lactam/β-lactamase inhibitor antibiotic combination approved in the European Union for treating multidrug-resistant infections, including metallo-β-lactamase-producing bacteria.¹

“For health care teams treating patients with serious gram-negative bacterial infections, the prospect of running out of effective treatment options is a daunting but very real threat,” said Yehuda Carmeli, head, National Institute for Antibiotic Resistance and Infection Control, Tel Aviv Medical Center, Israel, and an investigator in the REVISIT study. “The approval of Emblaveo is welcome news for the infectious disease community and provides new hope to critically ill patients affected by antimicrobial resistance.”¹

What the Data Demonstrated
The combination antibiotic combines aztreonam, a monobactam β-lactam, with avibactam, a recent broad-spectrum β-lactamase inhibitor. The combination of aztreonam with avibactam restores aztreonam’s activity against bacteria that co-produce MBLs and other β-lactamases.¹

This approval is based on results from the phase 3 program including the REVISIT and ASSEMBLE studies that looked at the efficacy, safety, and tolerability of aztreonam-avibactam in treating serious, gram-negative infections including MBL-producing multidrug-resistant pathogens for which there are limited or no treatment options.

The REVISIT study compared ATM-AVI ± metronidazole (MTZ) with meropenem (MER) ± colistin (COL) for the treatment of cIAI, HAP, and VAP. As previously reported by Contagion, the topline data from the study demonstrated:

• For patients with cIAI, cure rate in the intention to treat (ITT) analysis set was 76.4% (95% confidence interval (CI) [70.3, 81.8]) for the ATM-AVI ± MTZ treatment arm vs 74.0% (95% CI [65.0, 81.7]) for the MER ± COL treatment arm, with a treatment difference of 2.4% (95% CI [-12.4, 19.1]). In the clinically evaluable (CE) analysis set, cure rate was 85.1% (95% CI [79.2, 89.9]) for ATM-AVI ± MTZ versus 79.5% (95% CI [69.9, 87.1]) for MER ± COL.
• For patients with HAP/VAP, cure rate in the ITT analysis set was 45.9% (95% CI [34.9, 57.3]) for ATM-AVI ± MTZ versus 41.7% (95% CI [26.7, 57.9]) for MER ± COL, with a treatment difference of 4.3% (95% CI [-25.6, 32.2]). In the CE analysis set, cure rate was 46.7% (95% CI [32.7, 61.1]) for ATM-AVI ± MTZ vs 54.5% (95% CI [34.3, 73.7]) for MER ± COL.
• All-cause 28-day mortality rates were 4/208 (1.9%) for ATM-AVI ± MTZ versus 3/104 (2.9%) for MER ± COL in cIAI, and 8/74 (10.8%) for ATM-AVI ± MTZ versus 7/36 (19.4%) for MER ± COL in HAP/VAP.
• ATM-AVI ± MTZ was well-tolerated, with an overall observed pattern of treatment-emergent adverse events (TEAEs) in line with that described for aztreonam alone. The incidence of serious adverse events (SAEs) was similar between treatment groups (53 [19.3%] patients in the ATM-AVI ± MTZ group and 25 [18.2%] patients in the MER ± COL group). No patient treated with ATM-AVI ± MTZ experienced a treatment-related SAE.²

For the ASSEMBLE study, 5/12 (41.7%) of the ATM-AVI ± MTZ patients with infections due to confirmed MBL-producing Gram-negative bacteria were cured at TOC versus 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.²

The results overall showed that aztreonam-avibactam was well-tolerated, with no new safety findings and a similar safety profile to aztreonam alone.

With this approval, aztreonam-avibactam will be available in all 27 European Union (EU) member states, as well as in Iceland, Liechtenstein, and Norway. Pfizer is planning marketing authorization applications for the antibiotic in other countries including United Kingdom, China, and the US. No specific deadline was announced in this latest news.

References
1.European Commission Approves Pfizer’s EMBLAVEO for Patients with Multidrug-Resistant Infections and Limited Treatment Options.Pfizer press release.April 22, 2024. Accessed April 23, 2024.
https://investors.pfizer.com/Investors/News/news-details/2024/European-Commission-Approves-Pfizers-EMBLAVEO-for-Patients-with-Multidrug-Resistant-Infections-and-Limited-Treatment-Options/default.aspx

2.Pfizer Investigational Antibiotic Combination Demonstrates Efficacy Against Gram-Negative Infections. Contagion. June 14, 2023. Accessed April 23, 2024.
https://www.contagionlive.com/view/a-pfizer-investigational-antibiotic-combination-demonstrates-efficacy-against-gram-negative-infections