Gram-Negative NIs: Vabomere and the TANGO II Study

Peter L. Salgo, MD: Let’s talk about some pharmacy. Let’s talk about some new antibiotics. There was a 2017 approval of meropenem/vaborbactam. That’s Vabomere, right? What are the key findings from this study, TANGO II?

Jason Pogue, PharmD, BCPS-AQID: TANGO II is an interesting study because it’s the first real study that was trying to do a pathogen-directed study. So, when you see new drugs come to market, if it’s a gram-negative drug, it’s going to be studied in UTI and it’s going to be studied in intra-abdominal infections because that’s where gram-negatives cause problems.

But to Andy’s point from earlier, as much as it pains me to say it, people want to see data in the actual infections that they’re going to use the drug for. When you talk about a drug like meropenem/vaborbactam, it’s a hell of a CRE drug. It’s a great KPC (Klebsiella pneumoniae carbapenem)-active agent from that standpoint. So, people want to see how it fares in that situation. And so, what they did was a pragmatic study of patients who had either suspected or documented CRE infections. As you can imagine, that makes a mess of a clinical trial. There’s a reason people do UTI studies and intra-abdominal infection studies, because patients who have CRE, Andy listed all the risk factors for us. There’s a lot going on in that scenario. So, the numbers are very small, and the comparator group was actually kind of practical, where it was just the treating physician could ask, “What do I think the best antibiotics are? If they don’t get this new antibiotic, what’s my favorite cocktail to give them anyway?” And so, the numbers are very small, but even in that small cohort, you saw signals that it improved outcomes. You saw clinical care go up 30% to 35%; you saw suggestions of mortality decrease. And so, it’s a really cool type of trial, although they are extremely messy data to sift through.

Andrew Shorr, MD: I think the points about TANGO II that are also important to realize are it is a remarkably sick population. The mortality rate in that study is actually relatively high compared with what you see historically in the randomized, even nonblinded, trials in this disease state or in this space because most clinical trials exclude the sickest of the sick. And so this is fascinating because there are actually some real-world pragmatic data that the antimicrobial is effective in sick people. And in fact, if I’m remembering it correctly, TANGO II was terminated early because of benefit.

Jason Pogue, PharmD, BCPS-AQID: You’re right.

Andrew Shorr, MD: Again, to my recollection, never has a data safety monitoring board in antibiotic stopped a trial early for benefit. Now, I think there is another trial that’s done looking in kind of the same paradigm, the CARE study, with plazomicin. That’s about 28 patients, I think. TANGO II is a little bit bigger, with a 2:1 randomization. But the point is I think we’re finally beginning to see data emerge where they’re actually taking the drugs that are designed for specific pathogens and doing studies in populations and disease states that prove the drug doesn’t kill anybody, the drug does what it’s supposed to do, and then saying, “But no one is going to ever use this for empiric therapy in UTI, nor should they. And everybody would agree, so let’s go and prove to the doctor that this is going to work against the pathogen, in most cases in the blood, that we’re worried about.”