nacubactam (RG6080) / Roche, Meiji Seika - LARVOL DELTA

Outcomes of cefepime/nacubactam and aztreonam/nacubactam in cUTI/AP patients with ESBL-producing bacteria enrolled into prospective phase III randomised clinical study (Integral-1) (ESCMID Global 2026) - No abstract available

Clinical • P3 data

Population pharmacokinetic analysis of nacubactam, cefepime, and aztreonam and exposure–response analysis of efficacy results from phase III clinical trials (ESCMID Global 2026) - No abstract available

Clinical • P3 data • PK/PD data

Activity of the novel combination therapy cefepime/nacubactam against 17,220 clinical isolates of Enterobacterales collected worldwide during 2021-2024 (ESCMID Global 2026) - No abstract available

Clinical • Combination therapy

Efficacy and safety of cefepime/nacubactam and aztreonam/nacubactam vs best available therapy in adults with cUTI/AP, HABP/VABP, cIAI due to carbapenem resistant Enterobacterales: integral-2, single-blind, randomised phase III trial (ESCMID Global 2026) - No abstract available

Clinical • P3 data

Outcomes of cefepime/nacubactam and aztreonam/nacubactam for treatment of cUTI/AP patients with CRE: subgroup analysis of integral-1 study (ESCMID Global 2026) - No abstract available

Clinical

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 III trial (ESCMID Global 2026) - No abstract available

Clinical • P3 data • Infectious Disease • Nephrology

Determination of the nonclinical PK/PD target value for nacubactam in a mouse thigh infection model using carbapenem-resistant Enterobacterales under co-administration of cefepime or aztreonam (ESCMID Global 2026) - No abstract available

PK/PD data • Preclinical • Infectious Disease

Probability of target attainment of cefepime/nacubactam and aztreonam/nacubactam for carbapenem-resistant Enterobacterales infections (ESCMID Global 2026) - No abstract available

Infectious Disease

The in vitro activity of aztreonam/nacubactam and cefepime/nacubactam against molecularly characterised Enterobacterales isolates including those with ceftazidime-avibactam and aztreonam/avibactam resistance mechanisms collected globally from 2021-2023 (ESCMID Global 2026) - No abstract available

Preclinical

In vitro activity of nacubactam against broad-spectrum-ß-lactamases (ESCMID Global 2026) - No abstract available

Preclinical

Application of Epithelial Lining Fluid Drug Concentrations to MICi-Based PK/PD Modeling of Cefepime/Nacubactam in a Murine Model of CPE Pneumonia. (PubMed, J Infect Chemother) - "These findings support the utility of MICi-based PK/PD analysis for optimizing combination antibiotic therapy in pneumonia."

Journal • PK/PD data • Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases

Pharmacokinetics, safety, and tolerability of nacubactam (OP0595) after intravenous infusion: a randomized, double-blind, placebo-controlled phase I clinical trial in healthy Chinese male subjects. (PubMed, Clin Exp Med) - P1 | "Nacubactam, a novel β-lactamase inhibitor, combined with cefepime or aztreonam, effectively supports CRE infection treatment...Its combination with ceftazidime or aztreonam is promising for treating multidrug-resistant Gram-negative bacterial infections...In this work, we conducted a phase I randomized, double-blind, placebo-controlled trial to clinically evaluate nacubactam for the first time in healthy Chinese male subjects, demonstrating its good safety profile, dose-proportional pharmacokinetics, and mainly renal excretion. These data provide insights into the clinical application of nacubactam.Trial registration This trial was registered on the Chinese Clinical Trial Registration website, registration number ChiCTR2500103582."

Clinical • Journal • P1 data • PK/PD data • Infectious Disease

Integral-2: P3 Study to Assess Efficacy and Safety of Cefepime/Nacubactam and Aztreonam/Nacubactam Versus Best Available Therapy for Adults With Infection Due to Carbapenem Resistant Enterobacterales (clinicaltrials.gov) - P3 | N=126 | Completed | Sponsor: Meiji Seika Pharma Co., Ltd. | Recruiting ➔ Completed

Trial completion • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

Classification and applicability of new beta-lactamase inhibitors. (PubMed, Rev Esp Quimioter) - "This non-exhaustive minireview describes the main characteristics of the new beta-lactamase inhibitors (enmetazobactam, avibactam, relebactam, durlobactam, zidebactam, nacubactam, vaborbactam, taniborbactam, and xeruborbactam), their spectrum of inhibition, their activity in combination with different beta-lactams, the main resistance mechanisms that can compromise their activity and the main applications of the different beta-lactam-beta-lactamase inhibitor combinations depending on the type of beta-lactamase/carbapenemase and the microorganism involved."

Journal • Review

The Rapid CarbaLux Combination Test to Uncover Bacterial Resistance and Heteroresistance Prior to Antibiotic Treatment. (PubMed, Diagnostics (Basel)) - "It was expected that a specific inhibitor that protects imipenem or meropenem from enzymatic deactivation during antibacterial therapy would perform the same in vitro with fluorescent carbapenem and preserve its fluorescence. The new additional CarbaLux combination test is used if the classic test is positive for carbapenemases: a classic test tube pre-dosed with fluorescent carbapenem is spiked with cloxacillin; with recently launched carbapenemase inhibitors, e.g., avibactam, relebactam, zidebactam, nacubactam, or vaborbactam; or with picolinic acid...They are simpler, broader in scope, and more cost-effective; they can also detect antimicrobial heteroresistance or AmpC beta-lactamase hyperproduction, which is normally undetected when performing automated antibiotic susceptibility testing. The new tests are suitable for clinical diagnosis, public health purposes, and infection control."

Journal • Infectious Disease

Evaluation of in vitro efficacy of aztreonam-nacubactam and cefepime-nacubactam against clinical isolates of Stenotrophomonas maltophilia. (PubMed, Antimicrob Agents Chemother) - "While ATM-NAC showed more significant MIC reduction, FEP-NAC also remarkably decreased MICs, despite cefepime being a substrate for L1 β-lactamase. These findings suggest the potential of β-lactam-NAC combinations as promising alternatives, warranting further in vivo studies to confirm clinical applicability."

Journal • Preclinical

Electrostatic interactions influence diazabicyclooctane inhibitor potency against OXA-48-like β-lactamases. (PubMed, RSC Med Chem) - "Diazabicyclooctane (DBO) inhibitors, including avibactam and nacubactam, act on a wide range of enzymes to overcome β-lactamase-mediated resistance...Crystallographic and mass spectrometry data demonstrate that all three enzymes support desulfation of the bound DBOs. The results indicate that interactions with Arg214 affect DBO potency, suggesting that sequence variation in OXA-48-like β-lactamases affects reactivity towards inhibitors as well as β-lactam substrates."

Journal

Nacubactam (OP0595): a Novel Triple-Action Diazabicyclooctane in Combination with Cefepime or Aztreonam (IDWeek 2025) - No abstract available

Combination therapy • Infectious Disease

Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review. (PubMed, JAC Antimicrob Resist) - "A total of 191 articles addressing clinical research regarding the efficacy, safety, tolerability, and PK of new BL/BLI combinations with avibactam, durlobactam, enmetazobactam, nacubactam, relebactam, taniborbactam, tazobactam, vaborbactam and zidebactam were included...In spite of that, the development of new BLI effective for class B metallo-β-lactamases (MBL) is still challenging, being aztreonam/avibactam the only approved combination active against MBL-producing bacteria. Although there has been extensive research to develop new BLI and BL/BLI combinations, only a few have reached the market. More evidence of its usefulness in the real world is still needed."

Journal • PK/PD data • Review • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

Rapid emergence of resistance to broad-spectrum direct antimicrobial activity of avibactam. (PubMed, Microbiol Spectr) - "Avibactam (AVI) is a diazabicyclooctane (DBO) β-lactamase inhibitor used clinically in combination with ceftazidime...This activity has some mechanistic similarities to that of more potent novel DBOs (zidebactam and nacubactam) in late clinical development...We also found that bacteria with impairments in the stringent response could still develop resistance to AVI through different mutations. Our findings indicate the importance of studying how resistance will emerge to newer, more potent DBOs in development and early clinical use."

Journal • Infectious Disease

A randomized, double-blind, placebo-controlled Phase 1 study to evaluate the pharmacokinetic profile, safety and tolerability of Nacubactam administered by single and multiple intravenous infusions in healthy Chinese male subjects (ChiCTR) - P1 | N=20 | Completed | Sponsor: The Third Xiangya Hospital of Central South University; Meiji Seika Pharma Co., Ltd.

New P1 trial • Infectious Disease

Integral-2: P3 Study to Assess Efficacy and Safety of Cefepime/Nacubactam and Aztreonam/Nacubactam Versus Best Available Therapy for Adults With Infection Due to Carbapenem Resistant Enterobacterales (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Meiji Seika Pharma Co., Ltd. | Trial completion date: Feb 2025 ➔ Sep 2025 | Trial primary completion date: Feb 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

In vitro microbiological activity of aztreonam, cefepime and cefiderocol combined with nacubactam against NDM-harbouring Escherichia coli and Klebsiella pneumoniae clinical isolates (ESCMID Global 2025) - No abstract available

Late-breaking abstract • Preclinical • Infectious Disease • Pneumonia

Activity of the novel combination therapies cefepime/nacubactam against 12,613 clinical isolates of Enterobacterales collected worldwide during 2021-2023 (ESCMID Global 2025) - No abstract available

Clinical • Combination therapy

Genomic approach to evaluate the intrinsic antibacterial activity of novel diazabicyclooctanes (zidebactam and nacubactam) against clinical Escherichia coli isolates from diverse clonal lineages in the United Arab Emirates. (PubMed, J Infect Public Health) - "This study provides compelling evidence for the potential of DBOs, particularly zidebactam, as novel antibacterial agents. Their unique characteristics and broad-spectrum activity position them as promising candidates for future antibiotic development. While the inclusion of DBO therapies in the antibiotic arsenal could significantly impact MDR pathogen treatment, realizing their full potential requires further research, clinical evaluation, and vigilant monitoring of resistance mechanisms through integrated genomic approaches."

Journal