Meiji Seika Pharma: Positive Results from the Phase III Integral-1 Trial of Nacubactam, a Novel β-Lactamase Inhibitor, in Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis ― Published in The Lancet

TOKYO--(BUSINESS WIRE)--Meiji Seika Pharma Co., Ltd. (headquartered in Tokyo; President and Representative Director: Toshiaki Nagasato) today announced that the results of the Integral-1 study, one of two global Phase III clinical trials evaluating the efficacy and safety of its novel β-lactamase inhibitor nacubactam (development code: OP0595), have been published in The Lancet. The article is entitled “---Efficacy and safety of cefepime–nacubactam and aztreonam–nacubactam compared with imipenem–cilastatin for complicated urinary tract infection or acute uncomplicated pyelonephritis (Integral-1): a double-blind, randomised phase 3 trial” (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00596-9/fulltext)

Integral-1 is a global, double-blind, randomized Phase III trial (jRCT2031230075) in patients with complicated urinary tract infection or acute uncomplicated pyelonephritis that compared the efficacy and safety of nacubactam co-administered with either cefepime or aztreonam versus imipenem-cilastatin, a carbapenem. The study met its primary endpoint of composite clinical and microbiological response seven days after the end of treatment, demonstrating non-inferiority of cefepime-nacubactam to imipenem-cilastatin. Superiority of cefepime-nacubactam over imipenem-cilastatin and non-inferiority of aztreonam-nacubactam versus the same comparator were demonstrated. With respect to safety, the incidence of adverse events was comparable between groups, and no new safety concerns were identified.
Although not covered in this article, positive results were also observed in Integral-2, the other Phase III trial (jRCT2031230076) that enrolled patients with infections caused by carbapenem-resistant Enterobacterales (CRE). These results were presented at ESCMID Global 2026, and a manuscript is in preparation.

Carbapenem-resistant Gram-negative bacteria pose a global threat as carbapenems are among the last-resort options for severe infections. Effective agents against multidrug-resistant Gram-negative pathogens, including CRE, are urgently needed. To help address this need, in December 2025, Meiji Seika Pharma submitted an application in Japan for manufacturing and marketing approval of nacubactam and remains committed to contributing to global efforts against antimicrobial resistance (AMR)—the “silent pandemic.”

About nacubactam (development code: OP0595):

Nacubactam is a novel β-lactamase inhibitor discovered by Meiji Seika Pharma. In combination with existing β-lactam antibiotics, nacubactam is expected to be effective against carbapenem-resistant Enterobacterales (CRE). In addition, nacubactam inhibits penicillin-binding protein 2 (PBP2), an enzyme involved in the biosynthesis of peptidoglycan in the bacterial cell wall, the mechanism that distinguishes it from other β-lactamase inhibitors.