The US Food and Drug Administration has officially approved AbbVie’s EMBLAVEO™ (aztreonam and avibactam) as the first and only fixed-dose, intravenous, monobactam/β-lactamase inhibitor combination antibiotic.
According to certain reports, the stated drug was approved in combination with metronidazole, a combination geared towards patients aged 18 years and older who have limited or no alternative options for the treatment of complicated intra-abdominal infections (cIAI), including those caused by susceptible Gram-negative microorganisms. These microorganisms include Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens.
Staying on the point of Gram-negative infections for a second, they are understood to be among the biggest bottlenecks facing healthcare professional. This is largely because of their tendency to display antimicrobial resistance. You see, in 2021 alone, an estimated 1.14 million deaths globally were put down to bacterial AMR. Moving forward, If AMR continues to remain unaddressed, minor infections and routine surgical procedures can eventually become life-threatening or fatal, causing roughly-projected 39 million deaths by the year 2050.
AbbVie’s EMBLAVEO, in response, effectively combines aztreonam, a monobactam antibiotic, with avibactam which happens to be a β-lactamase inhibitor capable of protecting aztreonam from serine β-lactamase hydrolysis and restoring its activity against bacteria that co-produce Metallo-β-lactamases (MBLs) and serine β-lactamases.
In case you weren’t aware, MBLs translate to a type of enzyme produced by certain bacteria that can become resistant to antibiotics.
Anyway, FDA’s approval came on the back of a Phase 3 REVISIT study, where efficacy, safety, and tolerability of EMBLAVEO was analyzed in regards to treating serious infections due to Gram-negative bacteria, including MBL-producing multidrug-resistant pathogens, for which there are limited or no treatment options.
“As bacteria evolve, industry, government, and clinical experts must work together to ensure that the infectious disease community has the tools to advance public health,” said Roopal Thakkar, M.D., executive vice president, research & development, chief scientific officer, AbbVie. “We’re proud to offer this important novel treatment option to urgently address the significant threat of antimicrobial resistance.”
Talk about the stated trial on a slightly deeper level, it was a randomized, active-controlled, central assessor-blinded, multicenter trial designed to evaluate EMBLAVEO ± metronidazole versus the combination of meropenem ± colistin in patients who are suffering from cIAI or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia.
More on that would reveal how the study recruited 422 patients across 81 locations globally. Another detail worth a mention here is rooted in the primary endpoint here being a clinical cure at the test-of-cure visit in intent-to-treat (ITT) population.
As for the secondary endpoints, they included 28-day mortality in the ITT population, and safety across patients in the ITT population who received the study drug.
Among other things, we ought to mention that this trial included 312 hospitalized patients with cIAI, who were randomized 2:1 to receive treatment with EMBLAVEO with metronidazole or meropenem ± colistin for five to 14 days of therapy.
We must also touch upon FDA’s decision to grant Qualified Infectious Disease Product (QIDP) Designation and Fast Track Designation for EMBLAVEO back in 2019. The QIDP designation basically provides certain incentives for the development of new antibiotics, including priority review and eligibility for the FDA’s Fast Track Designation, and a five-year regulatory exclusivity extension.
On the other hand, Fast Track Designation is designed to facilitate the development, as well as accelerate their review, of drugs that promise to treat serious conditions with no sufficient treatment options.
“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,” said James A. McKinnell, M.D., infectious disease specialist, Milefchik-Rand Medical Group, Torrance Memorial Medical Center in Torrance, California. “The approval of EMBLAVEO provides physicians a much-needed therapeutic option to help address some of the most difficult antimicrobial-resistant pathogens and provides doctors an opportunity to treat patients with these challenging infections.”
