The phase 3 results for its antibiotic, cefepime-taniborbactam, demonstrated it met its primary endpoint and the company says it is on track for a fourth quarter 2022 FDA NDA.
Complicated Urinary Tract Infections (cUTI) can be very challenging for clinicians to treat. These UTI do not respond to traditional, first-line therapies, and due to the nature of these bacterial infections, and patients' frequent underlying health conditions, they can be more susceptible to complications including sepsis.
As there are a limited amount of efficacious therapies for these resilient infections, there is a clinical need for antibiotics.
Malvern, Pa.,-based Venatorx Pharmaceuticals has been developing its investigational antibiotic, cefepime-taniborbactam, for cUTI. And this morning, the company reported it had achieved its primary efficacy endpoint and demonstrated superiority to meropenem in its CERTAIN 1 phase 3 study evaluating cefepime-taniborbactam as a treatment for hospitalized adult patients with cUTI, including acute pyelonephritis.
“These data demonstrate that cefepime-taniborbactam represents a significant improvement over the standard of care and will support global health efforts to combat antibiotic-resistant infections,” Venatorx President and CEO Christopher J. Burns, PhD, said. “Cefepime-taniborbactam offers a new potential treatment option for patients with infections caused by highly resistant bacteria, even those resistant to widely used carbapenem antibiotics.”
The therapy combines cefepime, a well-established beta-lactam antibiotic with more than 2 decades of proven safety and clinical utility against susceptible gram-negative and gram-positive bacteria. Taniborbactam is a potent beta-lactamase inhibitor that, in combination with cefepime, offers a potential treatment option for patients with serious bacterial infections caused by difficult-to-treat drug resistant gram-negative bacteria, most notably carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA).
CERTAIN (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 study 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 as specified by FDA and European Medicines Agency guidance.
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 70.0% of cefepime-taniborbactam treated patients and 58.0% of meropenem treated patients (treatment difference 11.9; 95% confidence interval (CI), 2.4, 21.6).
A prespecified superiority test following confirmation of NI demonstrated the statistical superiority of cefepime-taniborbactam 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 were infrequent, occurring in 3.0% of cefepime-taniborbactam patients and 0.9% of meropenem treated patients.
Burns along with 2 other pharmaceutical veterans started the company in 2010, and the company name comes from the Latin word venator, which means hunter, and rx is the medical symbol for drugs.
Contagion interviewed Burns last fall who at that time spoke of the challenges of developing new, first in-class antibiotics for gram negative infections. He also noted that with bacterial infection resiliencies it is very difficult to make efficacious therapies that will last for a long time.
“We have all been looking for something brand new: new classes of drugs; new targets; new mechanisms of action,” Burns said during the interview. “For some of the key areas of need, which is in gram-negative infections, we have not been very successful.”
During the interview, he also discussed some of the issues associated with new drug development and what he said is, “innovative versus what’s considered derivative,” new therapies.
With the phase 3 results, the company is on track for a potential fourth quarter 2022 New Drug Application with the Food and Drug Administration.
“We plan to file a New Drug Application with the FDA for cefepime-taniborbactam for the treatment of cUTI later this year,” Burns said in the statement.