Venatorx Announces Presentation of Analysis of Cefepime-Taniborbactam in vitro Activity against Clinically Significant Gram-Negative Bacteria Isolated from Patients with Cancer at IDWeek 2023

In patients with cancer, the risk associated with infection-related death is over 2.9 times that estimated in the general population¹ and estimates from the Union International Cancer Control (UICC) indicate approximately 1 in 5 patients with cancer will require an inpatient admission due to an infection.² Infections due to gram-negative (GN) bacteria are increasing at many cancer centers across the US; in some centers, GN infections now represent the majority of infections identified.^3,4 In addition, cancer centers are also experiencing an increase in the number of infections attributed to a multi-drug resistant (MDR) GN bacteria^3,4 and, in one assessment across 231 facilities, patients with cancer (PWC) had 40-85% higher incidence of GN antimicrobial resistance (AMR) than in patients without cancer.⁵ The need for new antibacterial agents to address this emergence of MDR/AMR GN resistance at cancer centers is urgent.

The study, led by researchers from The University of Texas MD Anderson Cancer Center, assessed 270 recent GN clinical isolates from PWC.⁶ Numerous GN bacteria, including MDR GN bacteria were tested for susceptibility to cefepime-taniborbactam, an investigational antibiotic, and several currently available GN antibiotics such as ceftazidime-avibactam and ceftolozane-tazobactam which are currently being utilized for MDR GN infections. The bacterial isolates tested included Extended Spectrum β-lactamase (ESBL) producing Enterobacterales and Carbapenem Resistant Enterobacterales (CRE) isolates, and MDR Pseudomonas aeruginosa. In the study, cefepime-taniborbactam demonstrated higher in vitro activity than the tested comparators. While cefepime-taniborbactam has not yet been approved for clinical use, only 3 of the 270 isolates (1.1%; 2 CRE Escherichia coli and 1 MDR P. aeruginosa) were found to be resistant to cefepime-taniborbactam at its provisional breakpoint. The investigators concluded that cefepime-taniborbactam “has promising activity against clinically relevant GN bacterial pathogens isolated from PWC including MDR, CRE and ESBL.” The investigators also recommended additional studies to evaluate cefepime-taniborbactam against currently available antibiotics for GN infections with pathogens expressing serine and/or metallo‐ β‐lactamases in PWC.

About the CERTAIN-1 Phase 3 Clinical Trial

CERTAIN-1 (Cefepime Rescue with Taniborbactam in cUTI) was a global, randomized, double-blind, active-controlled non-inferiority Phase 3 study evaluating the efficacy, safety, and tolerability of cefepime-taniborbactam compared to meropenem in adults with cUTI, including acute pyelonephritis. The trial enrolled 661 adult patients who were randomized 2:1 to receive cefepime-taniborbactam 2.5g q8h or meropenem 1g q8h for 7 days (up to 14 days for patients with bacteremia). The primary efficacy endpoint evaluated the composite clinical and microbiologic response (i.e., bacterial eradication) at the Test of Cure (TOC) visit (Day 19-23) in the microbiological intent-to-treat (microITT) population.

Cefepime-taniborbactam met the primary efficacy endpoint of statistical noninferiority (NI) to meropenem in the microITT population at TOC with composite microbiologic and clinical success occurring in 70.6% of cefepime-taniborbactam treated patients and 58.0% of meropenem treated patients (treatment difference 12.6; 95% CI, 3.1, 22.2). A prespecified superiority assessment was conducted following confirmation of NI. The superiority of cefepime-taniborbactam was concluded as the lower bound of the 95% CI for noninferiority was greater than zero. The pre-specified superiority test (two-sided p-value = 0.0088) demonstrated the strength of evidence associated with the superiority conclusion for the composite endpoint at TOC. The superiority of cefepime-taniborbactam was sustained for the composite microbiologic and clinical response at the Late-Follow-Up (Day 28-35) visit.

Rates of treatment-emergent adverse events (TEAEs) were 35.5% for cefepime-taniborbactam and 29.0% for meropenem. Serious TEAEs occurred in 2.0% and 1.8% of cefepime-taniborbactam and meropenem treated patients, respectively. Treatment discontinuations due to TEAEs occurred in 3.0% of cefepime-taniborbactam patients and 0.9% of meropenem treated patients. There was one death in the cefepime-taniborbactam treatment group, which was unrelated to study treatment as assessed by the investigator.

About Cefepime-Taniborbactam

Cefepime-taniborbactam is an investigational intravenous (IV) beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotic combination being developed for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). The New Drug Application for cefepime-taniborbactam was accepted for review by the US FDA for cUTI, including pyelonephritis with a PDUFA date of February 22, 2024.

Cefepime, a fourth-generation cephalosporin, is a widely used beta-lactam (BL) antibiotic with more than two decades of proven safety and clinical utility against susceptible gram-negative and gram-positive bacteria. Taniborbactam is a beta-lactamase inhibitor (BLI) that, in combination with cefepime, is being studied as a potential treatment option for patients with serious bacterial infections caused by antibiotic resistant gram-negative bacteria, most notably Extended Spectrum Beta-lactamase (ESBL)-expressing Enterobacterales, Carbapenem-Resistant Enterobacterales (CRE), and Multidrug-resistant (MDR) Pseudomonas aeruginosa (MDR-PA), which can include Carbapenem-Resistant P. aeruginosa (CRPA).

Cefepime-taniborbactam has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the U.S. Food and Drug Administration (FDA).

Funding Partners and Collaborators

Development of cefepime-taniborbactam began with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract number HHSN272201300019C, and Wellcome Trust under award number 360G-Wellcome-101999/Z/13/Z, and continues with federal funds from the Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services under contract numbers HHSO100201900007C and 75A50122C00080.

In September 2018, Venatorx entered into an exclusive license agreement with Everest Medicines to support the development, registration, and commercialization of cefepime-taniborbactam in People’s Republic of China, Macau, Hong Kong, Taiwan, South Korea, and select countries in Southeast Asia (the “Territory”).

In April 2020, Venatorx and GARDP announced a collaboration to accelerate the development of, and access to, cefepime-taniborbactam for adult and pediatric populations. Venatorx has granted GARDP exclusive rights to distribute and sub-distribute cefepime-taniborbactam, once it is approved for clinical use, in low- and lower middle-income countries.

About Venatorx Pharmaceuticals, Inc.

Venatorx is a private, pre-commercial pharmaceutical company focused on improving health outcomes for patients with difficult-to-treat drug resistant gram-negative bacterial infections and viral infections. Venatorx’s lead asset, cefepime-taniborbactam, is an investigational antibiotic that completed a Phase 3 study (NCT03840148) in adults with complicated urinary tract infections (cUTI), including pyelonephritis and is under FDA review with a PDUFA action date of February 22, 2024. In October 2022, BARDA awarded a contract of up to $318M to Venatorx for development and procurement of cefepime-taniborbactam for the treatment of melioidosis and multidrug-resistant infections. As part of its broader pipeline, Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam etzadroxil, that recently completed multiple Phase 1 clinical studies and is expected to begin global Phase 3 testing in 2Q2025. For more information about Venatorx and its anti-infectives portfolio, please visit www.venatorx.com.

References

1. Zheng Y, et al. Infect Dis Ther. Jun 2021;10(2):871-895 doi:10.1007/s40121-021-00433-7
2. https://www.uicc.org/resources/amr-control-supplement; accessed Sept 27, 2023
3. Montassier E, Batard E, Gastinne T, Potel G, de la Cochetière MF. 2013. Recent changes in bacteremia in patients with cancer: a systematic review of epidemiology and antibiotic resistance. Eur J Clin Microbiol Infect Dis 32:841– 850. https://doi.org/10.1007/s10096-013-1819-7.
4. Rapoport B, Klastersky J, Raftopoulos H, Freifeld A, Aoun M, Zinner SH, Rolston KVI. 2016. The emerging problem of bacterial resistance in cancer patients; proceedings of a workshop held by MASCC “Neutropenia, Infection and Myelosuppression” Study Group during the MASCC annual meeting held in Berlin on 27–29 June 2013. Support Care Cancer 24:2819 –2826. https://doi.org/10.1007/s00520-016-3183-5.
5. Vikas Gupta, PharmD.; Kalvin C. Yu, MD, FIDSA; Charles Sheets, MS; Diane Flayhart, MS; and the Cancer & AMR Consortium. 2023. Burden of Antimicrobial Resistance in Hospitalized Patients with Cancer: A Multicenter Analysis (Poster 14) ASM/ESCMID 2023 Boston, MA (September 19-22)
6. Gerges BG, Rosenblatt j, Troung Y, Jiang Y, Hachem R, Chaftari A, Raad I. In Vitro Activity of Cefepime-Taniborbactam Against Clinically Significant Gram-Negative Bacteria Isolated from Patients with Cancer. (Poster 2122) IDWeek 2023 Boston, MA (October 11-15).

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