Meiji Seika Pharma’s Phase III Integral-2 trial showed improved treatment success with nacubactam combinations in carbapenem-resistant Gram-negative infections, with findings highlighted in The Lancet Microbe.
Written By: Mayuresh Salvi, PharmD
Reviewed By: Pharmacally Editorial Team
Meiji Seika Pharma has reported that results from its global Phase III Integral-2 trial evaluating nacubactam (OP0595) were highlighted in The Lancet Microbe‘s coverage of ESCMID Global Congress 2026, underscoring the investigational β-lactamase inhibitor’s potential to address difficult-to-treat carbapenem-resistant Gram-negative bacterial infections. The study met it’s prespecified objectives and supported the company’s ongoing regulatory efforts following its New Drug Application submission in Japan in December 2025.
Scientific and Clinical Context
Antimicrobial resistance (AMR), particularly resistance to carbapenems, remains one of the most pressing global public health threats. Carbapenem-resistant Enterobacterales (CRE) cause severe hospital-acquired infections and are associated with limited treatment options, high mortality, and prolonged hospitalization.
Nacubactam is a novel β-lactamase inhibitor that restores the activity of β-lactam antibiotics when combined with cefepime or aztreonam against resistant Gram-negative pathogens. Unlike currently available β-lactamase inhibitors, nacubactam also inhibits penicillin-binding protein 2 (PBP2), providing an additional antibacterial mechanism that enhances the activity of partner antibiotics against CRE. This dual mechanism distinguishes the investigational therapy from existing agents.
Phase III Integral-2 Trial Results
The Integral-2 study (jRCT2031230076) enrolled patients with complicated urinary tract infections (cUTIs), acute uncomplicated pyelonephritis, hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), and complicated intra-abdominal infections (cIAIs) caused by carbapenem-resistant Gram-negative bacteria, excluding Acinetobacter species.
The trial achieved its predefined study objectives. The primary endpoint, overall treatment success seven days after the end of therapy, was reached with:
- 0% (12/24) for aztreonam/nacubactam
- 4% (12/27) for cefepime/nacubactam
- 1% (6/23) for best available therapy (BAT)
Investigators also reported no major clinical safety concerns, supporting the tolerability profile of both investigational combinations.
According to The Lancet Microbe‘s ESCMID Global 2026 congress coverage, the findings represent an encouraging advance in the development of therapies targeting multidrug-resistant Gram-negative infections, an area where new treatment options remain urgently needed.
Development Program
Integral-2 complements the Integral-1 Phase III study (jRCT2031230075), which evaluated cefepime/nacubactam in patients with complicated urinary tract infections and acute uncomplicated pyelonephritis. Together, the two pivotal global studies formed the basis of Meiji Seika Pharma’s Japanese NDA submitted in December 2025.
Path Forward
Meiji Seika Pharma continues to position nacubactam as part of its strategy to address the growing burden of antimicrobial resistance. If approved, the agent could expand treatment options for infections caused by carbapenem-resistant Gram-negative pathogens by combining β-lactamase inhibition with direct PBP2 activity. Recognition of the Phase III data in The Lancet Microbe further highlights the clinical relevance of the Integral development program as regulatory review and future commercialization plans progress.
Reference
About the Writer
Mayuresh Sunil Salvi (Linkedin) is a PharmD professional and healthcare writer with a strong interest in pharmacovigilance, drug safety, and emerging medical research. He is passionate about exploring new drug discoveries, clinical research, and advances in evidence-based medicine. His interests also include ward rounds, prescription audits, and treatment analysis to support rational pharmacotherapy and improved patient care.