New antibiotic to combat infections caused by bacteria with multiple drug resistance

The European Medicines Agency (EMA) has recommended granting marketing authorization in the European Union (EU) for the drug Emblaveo (aztreonam-avibactam), intended for the treatment of complicated intra-abdominal and urinary tract infections, hospital-acquired pneumonia, and infections caused by certain types of bacteria (Gram-negative aerobes) when treatment options are limited.

Infections caused by Gram-negative bacteria resistant to many currently available antibiotics pose a serious public health problem as patients have limited or sometimes no treatment options available. Estimates suggest that infections caused by bacteria with multiple drug resistance are responsible for 35,000 deaths annually in the EU.

Emblaveo is a combination of two active substances with a fixed dose: aztreonam and avibactam. Aztreonam is already approved for use in the EU on its own, while avibactam is approved for use in combination with another antibiotic (ceftazidime). Aztreonam is an antibiotic belonging to the beta-lactam group. Avibactam inhibits the action of many bacterial enzymes called beta-lactamases. (see "Beta-lactamase inhibitors: classification, mechanism of action and clinical use")

These enzymes allow bacteria to break down beta-lactam antibiotics, such as aztreonam, making them resistant to the antibiotic. By blocking these enzymes, avibactam restores the activity of aztreonam against bacteria resistant to aztreonam. (see "Beta-lactamase Inhibitors: Classification, Mechanism of Action, and Clinical Application")

Emblaveo will be available for intravenous administration.

The Committee for Medicinal Products for Human Use (CHMP) of the EMA concluded that the benefits of Emblaveo outweigh its risks for patients with infections caused by Gram-negative bacteria when there are few or no therapeutic options available to combat the disease. Aztreonam has been shown to be effective in treating a range of serious infections. Microbiology data suggest that aztreonam in combination with avibactam will be effective in infections caused by many aerobic Gram-negative pathogens with multiple drug resistance, and therefore this combination may meet unmet medical needs.

Emblaveo underwent assessment under the accelerated assessment mechanism of the EMA as it is considered to be of significant interest to public health.

EMA recommendations are based on existing safety and efficacy data for each active substance, as well as the results of two phase III randomized trials submitted by the applicant. The studies were not designed to demonstrate efficacy, but provided safety and additional data for the combination. This aligns with EMA recommendations that allow a flexible approach to developing new antibiotics for human use targeting pathogens with multiple drug resistance for which new treatment methods are needed.

The most common side effects in patients taking Emblaveo were decrease in red blood cell count, elevated liver transaminase levels, and diarrhea. This aligns with documented safety information available for each individual substance.

The CHMP opinion is an intermediate step towards making Emblaveo available to patients. The conclusion will now be sent to the European Commission for a decision on granting marketing authorization in the EU. After marketing authorization is granted, pricing and reimbursement decisions will be made at the level of each member state considering the potential role or use of this drug within the national healthcare system of that country.

Note: The applicant for Emblaveo is Pfizer Europe Ma EEIG.

Source: https://www.ema.europa.eu/en/news/new-antibiotic-fight-infections-caused-multidrug-resistant-bacteri...