Pfizer receives positive CHMP opinion for the new antibiotic combination EMBLAVEO
Pfizer announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive marketing opinion for EMBLAVEO® (aztreonam-avibactam) in 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.
If approved, the drug will also be indicated for the treatment of infections caused by aerobic Gram-negative microorganisms in adult patients with limited therapeutic options. The Marketing Authorization Application (MAA) was examined under the accelerated assessment procedure, used by the CHMP when a pharmaceutical product is of high interest for public health and therapeutic innovation.
“Gram-negative bacteria are often resistant to multiple drugs, leaving infected patients severely ill and at high risk for serious complications, including mortality,” said James Rusnak, Senior Vice President and Chief Development Officer, Internal Medicine, Anti- Infectious Diseases and Hospitals, Pfizer. “If approved, aztreonam-avibactam could offer hope to adult patients with life-threatening Gram-negative bacterial infections, who currently have limited treatment options. This recommendation is a positive step for patients with nearly resistant Gram-negative bacterial infections. all available antibiotics and demonstrates Pfizer's commitment to helping address the global public health threat of antimicrobial resistance.”
Antibiotic resistance (AMR), particularly in Gram-negative bacteria, is a major threat to global health and the development of new treatments for infections caused by these bacteria has been highlighted as a key area by the World Organization of Health (WHO). A continued increase in antibiotic resistance could lead to 10 million deaths per year worldwide by 2050, and an estimated 1.27 million deaths globally were caused by bacterial antibiotic resistance in 2019 alone. Without solutions, the continued rise of antibiotic resistance could make routine medical procedures too risky.
The marketing authorization of aztreonam-avibactam includes previously reported positive results from the Phase 3 study program, including the REVISIT (NCT03329092) and ASSEMBLE (NCT03580044) studies, which evaluated efficacy, safety and tolerability of the drug in the treatment of serious bacterial infections due to Gram-negative bacteria, including multidrug-resistant metallo-β-lactamase (MBL)-producing pathogens for which therapeutic options are limited or absent. The data confirm that aztreonam-avibactam is effective and well tolerated, with no new safety findings and with a safety profile similar to that of aztreonam alone.
The European Commission (EC), which grants centralized marketing authorizations in the European Union (EU), will review the CHMP recommendation and is expected to make a final decision in the coming months. If granted, the centralized marketing authorization will be valid in all 27 EU Member States, as well as Iceland, Liechtenstein and Norway. Marketing authorization applications for aztreonam-avibactam are also expected to be submitted in other countries.
About EMBLAVEO® (aztreonam-avibactam)
If approved, aztreonam-avibactam will be indicated for the treatment of adult patients with complicated intra-abdominal infections (cIAI), hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), complicated urinary tract infections (cUTI ), including pyelonephritis, and infections due to aerobic Gram-negative microorganisms with limited therapeutic options. The drug combines aztreonam, a monobactam β-lactam, with avibactam, a broad-spectrum β-lactamase inhibitor.
Metallo-β-lactamases (MBLs) are a class of β-lactam enzymes that are not inhibited by current β-lactamase inhibitors and hydrolyze almost all β-lactam antibiotics, with the exception of monobactams such as aztreonam. However, monobactams are degraded by other β-lactamases that are often co-produced with MBLs, limiting the clinical utility of aztreonam monotherapy.
Combining aztreonam with avibactam restores aztreonam's activity against bacteria that coproduce MBL and other β-lactamases and, if approved, could provide an effective and well-tolerated therapeutic option against multidrug-resistant Gram-negative bacteria. These multi-resistant Gram-negative bacteria include MBL-producing Enterobacterales, which has been highlighted as a priority critical pathogen by WHO, and Stenotrophomonas maltophilia.
If approved, it would be the first β-lactam/β-lactamase inhibitor combination for the treatment of serious bacterial infections caused by multidrug-resistant Gram-negative bacteria, including MBL-producing bacteria, approved for use in the EU. The drug was jointly developed with AbbVie. Pfizer holds the global rights to commercialize this investigational therapy outside of the United States and Canada, where the rights are held by AbbVie. Its development was also supported by public-private partnerships between Pfizer and the US Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA) under OTA number HHSO100201500029C, and through the EU Innovative Medicines Initiative (IMI) – a partnership between the EU and the European pharmaceutical industry, under a project called COMBACTE-CARE (Combating Bacterial Resistance in Europe – Carbapenem Resistance).
The COMBACTE-CARE consortium is a first-of-its-kind public-private collaboration, combining the knowledge and skills of leading experts in drug-resistant bacterial infections and supported by the pan-European COMBACTE clinical and laboratory networks.
