FDA approves EMBLAVEO to combat complicated intra-abdominal infections with limited treatment options

The U.S. Food and Drug Administration (FDA) has granted approval for EMBLAVEO (aztreonam and avibactam), marking a significant milestone in the fight against complicated intra-abdominal infections (cIAI), particularly for adult patients who have limited or no alternative treatment options. This approval represents a pivotal development in addressing the growing global threat of Gram-negative bacterial infections, which are becoming increasingly resistant to current antimicrobial therapies.

Developed through a strategic partnership between AbbVie and Pfizer, EMBLAVEO is the first and only fixed-dose, intravenous combination of a monobactam antibiotic (aztreonam) and a broad-spectrum β-lactamase inhibitor (avibactam). This innovative antibiotic offers renewed hope for healthcare providers battling multidrug-resistant bacteria, filling a critical gap in infectious disease management.

What makes EMBLAVEO a breakthrough in treating complicated intra-abdominal infections?

EMBLAVEO’s approval is based on its unique formulation, which pairs aztreonam with avibactam. Aztreonam belongs to the monobactam class of antibiotics, effective against certain Gram-negative bacteria. However, its effectiveness is often compromised by β-lactamase enzymes, which break down antibiotics before they can combat bacterial infections. Avibactam counteracts this challenge by inhibiting these enzymes, effectively restoring aztreonam’s antimicrobial activity.

This combination therapy specifically targets bacteria that produce Metallo-β-lactamases (MBLs) and other β-lactamase enzymes. MBLs are particularly problematic because they are resistant to most β-lactam antibiotics, leaving few effective treatment options. EMBLAVEO’s ability to overcome these resistance mechanisms makes it a vital tool against Gram-negative bacterial infections such as those caused by Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens.

Why is antimicrobial resistance a growing global threat?

Antimicrobial resistance (AMR) is considered one of the most urgent public health threats worldwide. The overuse and misuse of antibiotics in healthcare and agriculture have accelerated the development of drug-resistant bacteria. According to global health projections, AMR could cause over 39 million deaths annually by 2050 if not addressed effectively. In 2021 alone, bacterial AMR was responsible for an estimated 1.14 million deaths globally.

The rise of AMR means that once-treatable infections are becoming increasingly deadly, leading to prolonged hospital stays, higher medical costs, and increased mortality rates. Routine surgeries, minor infections, and common diseases could become life-threatening without effective antibiotics. The approval of EMBLAVEO by the FDA underscores the urgent need for new antimicrobial therapies capable of addressing resistant bacterial strains.

How effective is EMBLAVEO based on clinical trial data?

The FDA’s decision was largely influenced by data from the Phase 3 REVISIT clinical trial, a robust, multinational, randomised, active-controlled study designed to assess EMBLAVEO’s efficacy and safety. The trial enrolled 422 patients across 81 global sites, comparing EMBLAVEO (with or without metronidazole) to a combination of meropenem (with or without colistin) in patients with cIAI and hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (though EMBLAVEO is not currently approved for pneumonia-related indications).

Among these participants, 312 hospitalised patients with complicated intra-abdominal infections were randomised in a 2:1 ratio to receive EMBLAVEO plus metronidazole or meropenem-based therapy for five to 14 days. The primary endpoint measured the clinical cure rate at the test-of-cure visit, while secondary endpoints evaluated 28-day mortality and safety profiles. EMBLAVEO demonstrated comparable efficacy and a favourable safety profile, reinforcing its potential as a reliable treatment option for drug-resistant infections.

What role do public-private partnerships play in developing new antibiotics?

The development of EMBLAVEO highlights the importance of public-private collaborations in tackling AMR. AbbVie and Pfizer co-developed the drug, with AbbVie holding commercial rights in the U.S. and Canada and Pfizer managing global markets. Additionally, the project received critical support from public health organisations, including the U.S. Department of Health and Human Services, the Biomedical Advanced Research and Development Authority (BARDA), and the European Union’s Innovative Medicines Initiative (IMI).

One notable partnership was with the COMBACTE-CARE consortium, a pan-European clinical and laboratory network focused on combating antibiotic resistance. This collaborative approach ensured access to cutting-edge research, extensive clinical trial networks, and expert knowledge in managing Gram-negative bacterial infections.

What do experts say about EMBLAVEO’s approval?

Infectious disease specialists have welcomed EMBLAVEO’s approval as a critical advancement in antimicrobial therapy. Dr. James A. McKinnell, an infectious disease expert at Milefchik-Rand Medical Group and Torrance Memorial Medical Center, emphasised the therapy’s significance:

“The continued evolution of antimicrobial resistance among Gram-negative bacteria has left some patients with little to no treatment options, resulting in extended hospital stays, additional morbidity, and death. The approval of EMBLAVEO provides physicians with a much-needed therapeutic option to address some of the most difficult antimicrobial-resistant pathogens.”

Dr. Roopal Thakkar, Executive Vice President of Research & Development and Chief Scientific Officer at AbbVie, echoed these sentiments, highlighting the urgent need for industry, government, and clinical experts to collaborate in developing innovative solutions for AMR.

What’s next for EMBLAVEO and its global rollout?

EMBLAVEO’s approval in the U.S. follows its prior regulatory successes in Europe and Great Britain. In April 2024, the European Commission granted marketing authorisation for EMBLAVEO for the treatment of cIAI, hospital-acquired pneumonia, ventilator-associated pneumonia, and complicated urinary tract infections (cUTI). By June 2024, Great Britain had also approved the therapy, with additional global regulatory submissions underway.

AbbVie plans to launch EMBLAVEO commercially in the U.S. during the third quarter of 2025. Its availability is expected to have a significant impact on clinical practices, providing healthcare professionals with a robust new option for managing infections caused by multidrug-resistant bacteria.