FDA approves drug combination for complicated intra-abdominal infections
AbbVie announced that the US FDA has approved aztreonam and avibactam (Emblaveo), in combination with metronidazole, for adults with complicated intra-abdominal infections who have limited or no alternative treatment options.
It is approved in combination with metronidazole, for patients 18 years and older who have limited or no alternative options for the treatment of complicated intra-abdominal infections (cIAI), including those caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens. Approval of this indication is based on limited clinical safety and efficacy data for EMBLAVEO. Gram-negative bacterial infections are among the most challenging for healthcare professionals to control due to high antimicrobial resistance (AMR).When AMR develops, medicines intended to treat these infections become ineffective, increasing the risk of morbidity and mortality.
"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."
AMR is considered an urgent global public health threat and could lead to over 39 million deaths worldwide by 2050. An estimated 1.14 million deaths globally were attributed to bacterial AMR in 2021 alone. If AMR remains unaddressed, minor infections and routine surgical procedures could become life-threatening or fatal. The FDA has prioritized the research and development of new medicines to treat AMR and help prevent the spread of infection.
"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."
EMBLAVEO is a medication that combines two components: aztreonam, a monobactam antibiotic, and avibactam, a β-lactamase inhibitor that protects aztreonam from serine β-lactamase hydrolysis and restores its activity against bacteria that co-produce Metallo-β-lactamases (MBLs) and serine β-lactamases. MBLs are a type of enzyme produced by certain bacteria that can become resistant to antibiotics and are on the rise globally.5 The approval of EMBLAVEO was supported by prior findings regarding the efficacy and safety of aztreonam for the treatment of cIAI. It was also supported by clinical trial results from the Phase 3 REVISIT study, which evaluated the efficacy, safety, and tolerability of EMBLAVEO for the treatment of serious infections due to Gram-negative bacteria, including MBL-producing multidrug-resistant pathogens, for which there are limited or no treatment options.
In 2019, the FDA granted Qualified Infectious Disease Product (QIDP) Designation and Fast Track Designation for EMBLAVEO. The QIDP Designation 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. The Fast Track Designation is designed to facilitate the development of and accelerate the review of drugs to treat serious conditions that do not have sufficient treatment options.
EMBLAVEO will be available for commercial use in the U.S. in Q3 2025.
About the Phase 3 REVISIT Study
The Phase 3 REVISIT clinical trial is a randomized, active-controlled, central assessor-blinded, multicenter trial evaluating EMBLAVEO ± metronidazole versus the combination of meropenem ± colistin in patients with cIAI or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (not an approved indication for EMBLAVEO). The study enrolled 422 patients across 81 locations globally. The primary endpoint was clinical cure at the test-of-cure visit in the intent-to-treat (ITT) population. Secondary endpoints included 28-day mortality in the ITT population, and safety in patients in the ITT population who received the study drug. The REVISIT trial included 312 hospitalized patients with cIAI that were randomized 2:1 to receive treatment with EMBLAVEO with metronidazole or meropenem ± colistin for five to 14 days of therapy. The trial was not designed with any formal hypotheses for inferential testing against the active comparator.
