FDA Approves Meropenem-Vaborbactam for Complicated UTIs

The US Food and Drug Administration (FDA) has approved meropenem-vaborbactam (Vabomere) as a treatment for adult patients with complicated urinary tract infections (cUTI), including those with pyelonephritis.

The approval was based on findings from the phase 3 TANGO-1 trial, which explored meropenem-vaborbactam in 545 patients with cUTI and acute pyelonephritis. In the study, the antibacterial regimen showed superior efficacy and comparable tolerability versus piperacillin/tazobactam (Zosyn).

Overall, at the end of intravenous therapy, 98.4% of those treated with meropenem-vaborbactam had either a cure or improvement in symptoms and a negative urine culture test compared with 94% of those treated with piperacillin/tazobactam (difference, 4.5%; 95% CI, 0.7%-9.1%). Seven days following treatment completion, 77% of those in the meropenem-vaborbactam arm had resolved symptoms and negative urine cultures versus 73% in the piperacillin/tazobactam group.

“The FDA is committed to making new safe and effective antibacterial drugs available,” Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval provides an additional treatment option for patients with cUTI, a type of serious bacterial infection.”

In the modified intention to treat analysis that was utilized for the approval, 272 patients received meropenem-vaborbactam and 273 got piperacillin/tazobactam. Both the antibiotic meropenem and the antiresistance agent vaborbactam were given at 2g intravenously for 3 hours every 8 hours for up to 10 days. Piperacillin was dosed at 4g and tazobactam was administered at 0.5g intravenously for 30 minutes every 8 hours. A test for cure was performed on day 15 to 19 and the last follow-up was on day 22 to 26.

At the time of the cure test, 374 patients were evaluable for assessment in a microbiologic intent to treat group (192 patients in the investigational group and 182 in the control). Overall, microbial eradication (pathogens reduced to <10³ CFU/ml) was seen for 66.7% of those in the meropenem-vaborbactam group versus 57.7% in the piperacillin/tazobactam arm (difference, 9.0%; 95% CI, -0.9% to 18.7%).

Overall, there were 347 microbiologic evaluable patients at the cure follow-up (178 vs 169 for the investigational and control arms, respectively). In this group, microbial eradication was seen for 66.3% and 60.4% of those treated with meropenem-vaborbactam and piperacillin/tazobactam, respectively (difference 5.9%; 95% CI, -4.2% to 16.0%).

Treatment emergent adverse events (TEAEs) were experienced by 39% of those in the meropenem-vaborbactam group versus 35.5% of those in the control arm. Drug-related TEAEs occurred in 15.1% of those in the investigational group versus 12.8% in the control. Overall, 2.6% of those in the meropenem-vaborbactam arm discontinued treatment due to an AE versus 5.1% with piperacillin/tazobactam. Serious AEs were similar between the two groups (4.0% vs 4.4%) as were deaths (0.7% each).

The most frequently observed AEs with meropenem-vaborbactam were headache, infusion site reactions, and diarrhea. Additionally, the FDA noted that meropenem-vaborbactam could be associated with allergic reactions and seizures and should not be used for patients with sensitivity to beta-lactams.

In addition to cUTI, the Medicines Company, which is the developer of meropenem-vaborbactam, is also exploring the fixed-dose antibiotic combination for carbapenem-resistant Enterobacteriaceae (CRE) infections of blood, lung, urinary tract, and abdominal organs. In July 2017, the company announced that the TANGO-2 study looking at the agent in CRE met its primary endpoint and that the study was being halted by an independent Data and Safety Monitoring Board.

In TANGO-2, meropenem-vaborbactam demonstrated improved clinical cure rates across all infection types compared with best available therapy. Moreover, there were reduced rates of renal adverse events with the combination. Findings from this trial have not yet been released.