Venatorx Pharmaceuticals is advancing the fight against difficult-to-treat, drug-resistant, gram-negative bacteria with a successful phase 3 clinical trial of its investigational antibiotic cefepime-taniborbactam.
Venatorx Pharmaceuticals announced successful phase 3 trial results for cefepime-taniborbactam, its investigational antibiotic aimed at treating complicated urinary tract infections.
The study included 661 hospitalized patients with complicated urinary tract infections, including acute pyelonephritis, receiving either 2.5 g of cefepime-taniborbactam or 1 g of meropenem every eight hours. The average age of study participants was 56.2 and 52.8% were female.
“In the CERTAIN-1 study, cefepime-taniborbactam achieved superiority to meropenem for the primary efficacy endpoint and sustained that clinical benefit versus meropenem up to 3 to 4 weeks after treatment ended,” Venatorx Pharmaceuticals CEO Chris Burns, PhD, told Contagion. “Cefepime-taniborbactam also showed numerical benefit vs meropenem in CERTAIN-1 against resistance mechanisms including: cefepime-resistant, multi-drug resistant (MDR) and extended-spectrum beta-lactamase (ESBL) pathogens. Additionally, cefepime-taniborbactam’s safety profile was consistent with meropenem and historical cefepime experience.”
The composite microbiologic and clinical response rate was 70.6% for cefepime-taniborbactam compared with 58% for meropenem at Day 19-23. At end of treatment (Day 7-14), response rates were 89.1% for cefepime-taniborbactam and 86% for meropenem, and at Day 28-35 they were 63.8% and 51.7% respectively.
Treatment-emergent adverse events occurred in 35.5% of patients in the cefepime-taniborbactam group and 29% of patients in the meropenem group, including headache, diarrhea, constipation, hypertension, and nausea.
“There were 2 pleasant surprises in CERTAIN-1,” Burns said. “First, one of the criteria of the study is that patients cannot be enrolled if their pathogens are resistant to either cefepime-taniborbactam or meropenem at baseline, so all pathogens were susceptible to both drugs at randomization. We were surprised that cefepime-taniborbactam was able to show sustained statistical superiority against meropenem at late follow-up (LFU) visit (Day 28-35), since other similar clinical trials in cUTI/AP have only shown non-inferiority at this time point 3-4 weeks after study drug was stopped.
“Secondly, some other similar clinical trials in cUTI/AP have been able to show statistical significance against the comparator at Test of Cure (TOC) visit (Day 19-23), which was driven by the microbiological component of the composite endpoint and we did as well. When cefepime-taniborbactam showed statistical significance to meropenem at LFU as well, we were pleased to see that the clinical response component of the composite endpoint was also statistically significant, which was very fortunate. No other similar clinical trials in cUTI/AP have shown this clinical benefit at this later LFU timepoint.”
About 42% of study participants were diagnosed with acute pyelonephritis and 58% with cUTI. Most (97.5%) had monomicrobial gram-negative infections. Enterobacterales made up most infections, including Enterobacter cloacae complex (3.4%), Escherichia coli (69%), Klebsiella pneumoniae (13.8%) and Proteus mirabilis (4.6%). Pseudomonas aeruginosa was identified among 4.1% of participants.
Among study participants with cefepime-resistant pathogens, response rates were 70.8% in the cefepime-taniborbactam group and 53.3% in the meropenem group. Response rates for those with extended-spectrum beta-lactamase-producing (ESBL) pathogens were 68.6% and 57.1% respectively and for multidrug-resistant pathogens, response rates were 67% and 58.9% respectively.
“We believe these data could support an approval of cefepime-taniborbactam which may provide a new option for health care professionals to address the devastating impact on patient lives from the growing global pandemic of difficult-to-treat drug resistant gram-negative bacterial infections,” Burns said. “Venatorx continues to support antibiotic research with multiple programs focused on improving health outcomes for patients with difficult-to-treat drug resistant gram-negative bacterial infections and viral infections.”
The company plans to submit a New Drug Application in the first half of 2023.