Peter L. Salgo, MD: Let’s look down the pipeline a little further. Bezlotoxumab—a biologic. Is anybody familiar with that?
Dale N. Gerding, MD: It is a passive antibody approach that directs the antibody at the toxin for Clostridium difficile. It happens to target just the toxin B. It’s bezlotoxumab, but I think it’s quickly going to go by the name “Bezlo” because no one can pronounce it, including me. Its mechanism of action is that it is able to bind toxin, although it’s given intravenously. So, this is an infusion. But in the circulation, the antibody can cross over through the damaged mucosa of the colon and then locate the toxin in the lumen and bind to it and prevent the symptoms of disease. It does not do anything to the organism, nor does it do anything for the microbiota. But it allows the Clostridium difficile to eventually go away and the microbiome to recover. And its indication for use is to prevent recurrence. That’s its sole indication.
Peter L. Salgo, MD: You don’t give it acutely. You give it to prevent recurrence?
Dale N. Gerding, MD: Yes. You have a patient who’s being treated for Clostridium difficile with antibiotics, and you add this intravenous infusion to reduce the risk that the patient will have a recurrence.
Peter L. Salgo, MD: So, if I understand you correctly, it’s an anti-toxin.
Dale N. Gerding, MD: That’s correct. Exactly.
Peter L. Salgo, MD: And nobody thought of this before because?
Dale N. Gerding, MD: Oh, it’s been thought of before.
Erik Dubberke, MD: Yes. Some people have used intravenous immunoglobulin, where there are anti-Clostridium difficile toxin antibodies in IVIG (intravenous immunoglobulin). This is just a monoclonal antibody—so, there is a very high concentration of antibodies against toxin B.
Yoav Golan, MD, MS: The difference is that this one works.
Peter L. Salgo, MD: We’ve had lots of trials in the past.
Yoav Golan, MD, MS: Right, but this one works. In the beginning, there was an antibody against toxin A in the mixture. It was proven to not work even though it was a targeted antibody. But this one does work, and this one will likely be used in patients.
It’s hard to imagine that everyone with Clostridium difficile will get this infusion, because, as we’ve heard, many of the patients who are diagnosed with Clostridium difficile are diagnosed in the community. But, again, there are populations that are at risk for recurrence. And, as we mentioned, the most well-defined populations are those who already had Clostridium difficile in the past. So, this will likely be used in people who had Clostridium difficile in the past (maybe one episode of Clostridium difficile) and have another risk factor, such as age.
Dale N. Gerding, MD: It’s been shown to work just as well in high-risk patients over the age of 65, carriers of the epidemic strain 027, patients who are immunocompromised, and even in combinations of those high-risk factors. And I think those are going to be the most likely targeted patient groups.
Lawrence J. Brandt, MD: If this were cheap, would you not give it to everybody?
Dale N. Gerding, MD: I think we can say that about a lot of things. We don’t know what pricing will be. It’s not expected to be marketed until next year.
Lawrence J. Brandt, MD: Without cost, would it not make sense to have something there that can bind to the toxin, maybe shorten the natural history of the disease episode, and hang around? And you can prevent recurrence in everybody?
Dale N. Gerding, MD: It will reduce recurrence, but not completely eliminate it. I don’t want to be misleading anyone in thinking this will end recurrences. It reduces them from about 27% in the placebo group down to 17%.
Peter L. Salgo, MD: That’s significant.
Dale N. Gerding, MD: It’s definitely a significant reduction. There still will be people having recurrences, and, of course, the less expensive the drug is, the more it would be used, undoubtedly. But this is also going to be a drug, presumably, that has a fairly high cost of gross and development.
Peter L. Salgo, MD: But you can get permanent injury to the colon and persistent diarrhea going forward. And, presumably, at least part of this permanent damage is due to the chronic exposure to the toxin. Taking the toxin away, binding it, and keeping it away from the gut can’t be bad. You might reduce this 25% a lot.
Dale N. Gerding, MD: Absolutely.
Erik Dubberke, MD: But I think one thing to keep in mind with the discussion is that if just giving bezlotoxumab to everyone, it remains to be seen if it was just a statistical anomaly. The numbers were very small, but it did appear that there may have been an increased risk of adverse events amongst people with congestive heart failure who received the drug. So, maybe that’s one population to be a little more cautious with. If it’s someone who’s had 3, 4, or 5 episodes of Clostridium difficile, then the risk-benefit is probably there.
Daniel E. Freedberg, MD, MS: That makes sense. But, like IVIG, which also can cause some volume shifts, it might cause a little bit of...
Erik Dubberke, MD: Yes, it remains to be seen. So, we will know more once it gets used a little more in clinical practice and we have some more experience.