TOKYO, Japan, May 15, 2026
Meiji Seika Pharma Co., Ltd. announced that positive results from the global Phase III Integral-1 clinical trial evaluating its novel β-lactamase inhibitor nacubactam (OP0595) have been published in The Lancet. The study demonstrated that the investigational combination therapies cefepime-nacubactam and aztreonam-nacubactam showed strong efficacy and safety in patients with complicated urinary tract infections (cUTI) and acute uncomplicated pyelonephritis (AUP), while also addressing the growing global threat of antimicrobial resistance (AMR).
The Integral-1 trial was a global, double-blind, randomized Phase III study comparing nacubactam-based combinations against the carbapenem antibiotic imipenem-cilastatin, which is commonly used as a last-resort treatment for severe multidrug-resistant bacterial infections. Researchers reported that the study successfully met its primary endpoint, demonstrating non-inferiority of cefepime-nacubactam versus imipenem-cilastatin in achieving combined clinical and microbiological response seven days after treatment completion. Importantly, cefepime-nacubactam also demonstrated superiority over imipenem-cilastatin, while aztreonam-nacubactam achieved non-inferiority against the comparator therapy. Safety analysis showed comparable adverse event rates across treatment groups with no new safety concerns identified.
Nacubactam Targets Drug-Resistant Gram-Negative Infections
According to Meiji Seika Pharma Co., Ltd., nacubactam is a next-generation β-lactamase inhibitor designed to restore the activity of existing β-lactam antibiotics against highly resistant bacteria, including carbapenem-resistant Enterobacterales (CRE). CRE pathogens are considered among the most dangerous multidrug-resistant organisms globally due to their resistance to carbapenems, one of the last effective antibiotic classes available for severe infections.
What differentiates nacubactam from traditional β-lactamase inhibitors is its additional ability to inhibit penicillin-binding protein 2 (PBP2), an enzyme involved in bacterial cell wall biosynthesis. This dual mechanism may provide enhanced antibacterial activity and broader effectiveness against difficult-to-treat Gram-negative pathogens. Researchers believe this unique mechanism could strengthen the fight against resistant infections while helping reduce dependence on carbapenem antibiotics.
Growing Focus on Antimicrobial Resistance Solutions
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The publication of the Integral-1 data comes as global healthcare systems continue facing rising concerns over antimicrobial resistance, often described as the “silent pandemic.” Multidrug-resistant Gram-negative bacteria have become a major public health threat, increasing mortality rates, healthcare costs, and treatment complexity worldwide. Meiji Seika Pharma stated that positive findings were also observed in the separate Integral-2 Phase III trial, which specifically enrolled patients with infections caused by carbapenem-resistant Enterobacterales. Those results were previously presented at ESCMID Global 2026, with a full manuscript currently in preparation.
In December 2025, the company submitted a manufacturing and marketing approval application for nacubactam in Japan, signaling continued progress toward potential commercialization. If approved, nacubactam-based therapies could provide physicians with an important new treatment option against serious resistant bacterial infections while supporting global AMR containment efforts.
Source: Meiji Seika Pharma press release
