The European Medicines Agency (EMA) has issued a positive opinion on the marketing authorization of Emblaveo (Aztreonam-Avibactam), recommended for the treatment of complicated intra-abdominal and urinary tract infections, hospital-acquired pneumonia, and infections caused by certain bacteria species (aerobic gram-negative) where therapeutic options are limited.
In 2020, the World Health Organization and the European Center for Disease Prevention reported over 670,000 cases of antibiotic-resistant bacterial infections in the European Union/ European Economic Area, resulting in approximately 33,000 deaths.
Emblaveo underwent an accelerated review process by the EMA due to its significant public health importance.
Mechanism of Action
The fixed-dose combination will soon be available as an intravenous infusion.
Emblaveo combines Aztreonam and Avibactam; Aztreonam, an established antibiotic in the EU from the Beta-Lactam group, prevents bacteria cell wall formation. Avibactam, also approved in combination with Ceftazidime, inhibits Beta-Lactamases that break down antibiotics like Aztreonam, restoring its effectiveness against resistant bacteria.
Evidence
EMA’s endorsement of Emblaveo is based on existing safety and efficacy data for its active components and results from two randomized Phase-3 studies: REVISIT and ASSEMBLE.
The REVISIT study included individuals from regions with suspected multi-resistant pathogens and endemic or emerging carbapenem resistances. 422 hospitalized adults with complicated intra-abdominal infections (cIAI), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) were recruited. Patients received Emblaveo with or without Metronidazole.
For patients with cIAI, the Emblaveo regimen showed a healing rate of 76.4%, compared to 74.0% in patients treated with Meropenem with or without Colistin. The corresponding healing rates for HAP and VAP were 45.9% and 41.7% for Emblaveo and Meropenem therapies, respectively. Although Emblaveo showed better healing rates in both cases, the treatment effect did not reach statistical significance.
Emblaveo was well-tolerated, with similar occurrence of severe adverse events between the treatment and control groups. Side effects included decreased red blood cell count, elevated liver enzyme levels, and diarrhea, consistent with the known effects of Aztreonam alone. No serious toxicities were attributed to the study treatment.
The ASSEMBLE study subsequently confirmed these results, focusing on patients hospitalized for metallo-beta-lactamase-producing gram-negative bacteria. The Emblaveo regimen achieved a healing rate of 41.7% in treated patients, while none of the patients receiving the best available therapy were cured.
Although these studies were not primarily focused on proving efficacy, they contribute to the safety and supplementary insights into the combination. This approach aligns with EMA guidelines, allowing flexibility in the development of new antibiotics against multi-resistant pathogens.
The opinion will now be forwarded to the European Commission for review in granting EU-wide marketing authorization.