Meiji Seika Pharma Co., Ltd. (headquartered in Tokyo, President and Representative Director Toshiaki Nagasato) announced today that results from the global Phase III Integral-2 study of nacubactam (development code: OP0595), a novel β-lactamase inhibitor, were highlighted in The Lancet Microbe’s coverage of the ESCMID Global Congress 2026, held in Munich, Germany.
As presented in the The Lancet Microbe report, the key findings disclosed by Meiji Seika Pharma at the ESCMID Global Congress 2026 are as follows:
The Integral-2 study (jRCT2031230076) is a global Phase III clinical trial enrolling patients with complicated urinary tract infections (cUTI), acute uncomplicated pyelonephritis (AUP), hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), or complicated intra-abdominal infections (cIAI) caused by carbapenem-resistant Gram-negative bacteria (excluding Acinetobacter species). The study achieved its prespecified endpoints. For the primary endpoint of overall therapeutic success seven days after the end of treatment, the success rates were 44.4% (12/27 patients) for cefepime/nacubactam and 50.0% (12/24 patients) for aztreonam/nacubactam. For comparison, the success rate for best available therapy (BAT) was 26.1% (6/23 patients). No major clinical safety concerns were observed.
Nacubactam is a β-lactamase inhibitor designed for use in combination with cefepime or aztreonam to treat infections caused by carbapenem-resistant Gram-negative bacteria. Based on the results of two global Phase III studies – the Integral-1 study (enrolling patients with cUTI and AUP; jRCT2031230075) and the Integral-2 study (patients with infections due to carbapenem-resistant Enterobacterales [CRE]; jRCT2031230076) – Meiji Seika Pharma filed a New Drug Application (NDA) in Japan in December 2025.
Antimicrobial resistance (AMR) has been recognized by the World Health Organization as one of the top global public health threats. The rise of carbapenem-resistant pathogens, particularly Enterobacterales, has severely limited treatment options. Nacubactam belongs to a new generation of β-lactamase inhibitors that combine the ability to inhibit both serine and metallo-β-lactamases with direct anti-bacterial activity through binding to penicillin-binding protein 2 (PBP2). This dual mechanism makes nacubactam distinct from existing inhibitors such as avibactam, vaborbactam, or relebactam, which do not possess intrinsic antibacterial activity. By restoring the activity of β-lactam antibiotics against resistant pathogens, nacubactam has the potential to address a critical unmet medical need.
The Integral-2 study enrolled a diverse patient population across multiple countries, including centers in North America, Europe, and Asia. The inclusion of patients with various infection types (cUTI, AUP, HABP, VABP, cIAI) reflects the real-world challenge of managing carbapenem-resistant infections, which can affect multiple organ systems. The success rates observed with both cefepime/nacubactam and aztreonam/nacubactam were numerically higher than those of the BAT comparator, although the sample sizes were relatively small due to the difficulty of enrolling patients with confirmed carbapenem-resistant infections. The safety profile was consistent with that of the component antibiotics, with no unexpected adverse events. Common side effects included mild gastrointestinal disturbances, headache, and injection site reactions, but no treatment-related mortality was reported.
Meiji Seika Pharma has been at the forefront of anti-infective research for decades. The company's pipeline includes several novel agents targeting multidrug-resistant Gram-negative bacteria. Nacubactam was originally discovered by Meiji Seika through a screen for compounds that could inhibit β-lactamases and simultaneously bind to PBP2. The compound entered clinical development in the early 2020s, with Phase I studies demonstrating favorable pharmacokinetics and tolerability. The Integral-1 study, which focused on cUTI and AUP, met its primary endpoint of non-inferiority compared to standard therapy, further supporting the regulatory submission.
The Lancet Microbe, a leading journal in the field of infectious diseases and microbiology, selected the Integral-2 results for special coverage during the ESCMID Global Congress, underscoring the significance of the data. ESCMID (European Society of Clinical Microbiology and Infectious Diseases) is one of the world’s largest professional societies in infectious diseases, and its annual congress attracts thousands of clinicians, researchers, and industry professionals. The highlight in The Lancet Microbe provides additional visibility and credibility to the findings.
The NDA submitted in Japan covers the use of nacubactam in combination with cefepime or aztreonam for the treatment of infections due to carbapenem-resistant Gram-negative bacteria. Regulatory reviews in other regions, including the United States and Europe, are expected to follow, pending additional data or bridging studies. The company is also exploring the use of nacubactam in combination with other β-lactam antibiotics to broaden its clinical utility.
Antibiotic resistance, often called the silent pandemic, is responsible for more than 1.2 million deaths annually worldwide, with projections exceeding 10 million by 2050 if no effective interventions are implemented. Novel agents like nacubactam are essential to combat this trend. The dual mechanism of nacubactam not only addresses resistance mediated by β-lactamases but also offers a direct antibacterial effect, which may be particularly valuable in situations where resistant subpopulations emerge during therapy. This attribute differentiates nacubactam from other β-lactamase inhibitors that solely rely on protecting the partner antibiotic.
In addition to the Integral studies, Meiji Seika Pharma is conducting preclinical investigations of nacubactam in combination with various cephalosporins and carbapenems. Early data suggest that the combination with cefepime covers a broad spectrum of Gram-negative pathogens, including those producing ESBLs, AmpC enzymes, and carbapenemases of both serine and metallo types. The aztreonam combination is especially useful for infections caused by metallo-β-lactamase producers, such as New Delhi metallo-β-lactamase (NDM), against which many other β-lactam/β-lactamase inhibitor combinations are inactive.
The Lancet Microbe coverage highlighted the Integral-2 results in the context of the ongoing battle against AMR. The journal’s editors noted that the high success rates of the nacubactam combinations compared to BAT represent a promising step forward. However, they also cautioned that further studies with larger sample sizes are needed to confirm the findings and to assess the potential for resistance development over time. Nevertheless, the data have been met with enthusiasm by the infectious disease community, which has few therapeutic options for carbapenem-resistant infections.
Meiji Seika Pharma reaffirms its commitment to contributing to the fight against antimicrobial resistance. The company continues to invest in R&D for new antibiotics and alternative therapies, including phage therapy and immunomodulators. The advancement of nacubactam to regulatory submission marks a significant milestone in this endeavor.
The source language of the original text is German, but the official and authorized version is the English translation. For legal purposes, only the original language version of the publication is binding. Therefore, translations should be compared with the original language version of the publication.
Source:Afp News