The European Medicines Agency (EMA) has adopted a positive opinion for the marketing authorization of Emblaveo (aztreonam-avibactam), recommended for treating complicated intra-abdominal and urinary tract infections, hospital-acquired pneumonia, and infections stemming from specific types of bacteria (aerobic gram-negative) where therapeutic choices are restricted.
The World Health Organization and European Centre for Disease Prevention have reported that in 2020, more than 670,000 drug-resistant bacterial infections occurred in the European Union/European Economic Area alone, resulting in approximately 33,000 deaths.
The antibiotic was evaluated through the EMA’s accelerated assessment process owing to its significant public health relevance.
Mode of ActionThe fixed-dose combination will soon be accessible as an intravenous infusion.
Emblaveo combines aztreonam and avibactam; aztreonam is an established EU-approved antibiotic from the beta-lactam group that bacterial cell wall formation. Avibactam, also approved but in combination with ceftazidime, inhibits beta-lactamases that break down antibiotics like aztreonam thus restoring its effectiveness against resistant bacteria.
The EvidenceEMA’s endorsement of Emblaveo is grounded on existing safety and efficacy data for its active components, alongside findings from two phase 3 randomized trials: REVISIT and ASSEMBLE.
The REVISIT trial enrolled people from regions where there is suspicion of multidrug-resistant pathogens and endemic or emerging carbapenem resistance. It recruited 422 hospitalized adults with complicated intra-abdominal infections (cIAI), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Patients received Emblaveo with or without metronidazole.
In patients with cIAI, the Emblaveo regimen demonstrated a cure rate of 76.4%, compared with 74.0% for those treated with meropenem with or without colistin. For HAP and VAP, the corresponding cure rates were 45.9% and 41.7% for Emblaveo and meropenem regimens, respectively. Although Emblaveo showed superior cure rates in both cases, the treatment effect did not reach statistical significance.
Emblaveo was found to be well tolerated, with a balanced occurrence of serious adverse events between treatment and control groups. Side effects include decreased red blood cell count, elevated liver transaminase levels, and diarrhea, consistent with known effects of aztreonam alone. No serious toxicities were attributed to the study treatment.
The ASSEMBLE study subsequently corroborated these findings, focusing on patients hospitalized for metallo-beta-lactamase–producing gram-negative bacteria. The Emblaveo regimen achieved a cure rate of 41.7% among treated patients, whereas none of those receiving the best available therapy were cured.
Though these trials were not primarily designed to demonstrate efficacy, they contribute safety and supplementary insights into the combination. This approach aligns with EMA’s guideline, allowing flexibility in developing new antibiotics targeting multidrug-resistant pathogens.
The opinion will now be forwarded to the European Commission for consideration in granting EU-wide marketing authorization.
Source : Medscape