Novel Treatment Extends Time to Recurrence in Patients With C. Difficile

In an interview with Pharmacy Times, Paul Feuerstadt, MD, FACG, AGAF, discussed the investigative C. difficile treatment RBX2660 and how it impacts time to recurrence.

Q: In addition to reducing the recurrence of C. difficile, why is it important to research the time to recurrence?

Paul Feuerstadt, MD, FACG, AGAF: You know, this is a really important question and one of the controversies over the last, I'll say, 10 to 15 years in the C. difficile world. What defines a recurrence? Is it 30 days? Is it 60 days? Is it 90 days? Is it 6 months? And when you review the foundational trials, there's a lot of heterogeneity there. The fidaxomicin pivotal trial in the New England Journal of Medicine with Tom Louis as the first author from 2011 had a 25-day follow-up. However, all of the microbiota-based live biotherapeutic products, including RBX2660, have an 8-week follow up. So, we really settled on 8 weeks as being that compromise between 1 month and 3 months, really.

But what we've seen through these clinical trials is that the majority of patients that recur, they recur within 4 weeks. And that is very consistent within a number of other trials, both considering RBX2660, but also foundational trials considering fecal microbiota transplant in general. So, within this trial, and within this abstract, what was looked at was the 25th percentile time to recover through a Kaplan-Meier analysis. And what they found was, yes, the majority of recurrences within the phase 3 PUNCH CD3 trial considering RBX2660 head-to-head with placebo, the majority happened within 4 weeks. But the 25th percentile for the placebo arm was 14 days, whereas with RBX2660, it was 30 days. Importantly, that was consistent with the phase 2 trial data Kaplan-Meier analysis of similar structure.

So why is that important? The reason that that's important is when we give a placebo, we're not supplementing anything, so you wouldn't expect colonization resistance to gain any strength from that. And that's what you see 14 days there recurring. Whereas when RBX2660 was used, you see a 30-day 25th percent recurrence. What that speaks to is, yes, there was some supplementation, but it might not have been enough in that small group of patients that recurred. So, what you might hypothesize is by using a second treatment in the future that would further fortify the microbiota and decrease future occurrence.

Q: How did treatment with RBX2660 impact time to recurrence?

Paul Feuerstadt, MD, FACG, AGAF: So really, the time to recurrence was longer with RBX2660, speaking to the fact that it did fortify the microbiota, and it did supplement some of the deficiencies and it created an environment that was more resistant to recurrence.

Q: How could this finding impact patients’ quality of life and other outcomes?

Paul Feuerstadt, MD, FACG, AGAF: So, I mean, in general, when you talk about a product like RBX2660, in reducing recurrence that has a significant impact on patient's quality of life. We did a study a couple of years ago that was published in 2020. It was a survey looking at 350 total individuals, and one-third of them had active C. difficile, meaning they had it at the time they completed the survey, and two-thirds of them had a distant history, meaning more than 3 months in the past. And we asked them about the physical symptoms of C. difficile, the abdominal pain, the diarrhea, the fevers, the sweats, the fatigue, and we also ask them about the psychological impact, anxiety, depression, post-traumatic stress disorder. We ask them about the adaptational effect of C. difficile—have they changed how they live their lives? Do they change what they eat? When they eat, how they eat? Do they bring a pack of clothes with them in the event that they have an accident? We ask them about their relational impact. Do they feel comfortable going out and socializing with other people? And finally, the productivity element, which is are they comfortable going to work? Are they able to go to work?

And it turns out for the physical, psychological, adaptational, and relational, more than 50% of patients with active C. difficile and with a distant history are impacted in a significant way. And for productivity about 51% with active C. difficile were impacted with active infection, whereas 33% were impacted with a distant history. So, we can see just how all-encompassing this is. And products like RBX2660 can go a long way in reducing recurrence. And I think reducing that impact on these patients’ quality of life, giving them more confidence, less likely to having to adapt in significant ways, be more comfortable going out socially, and honestly earning a living.

Q: Is there anything you want to add?

Paul Feuerstadt, MD, FACG, AGAF: You know, this poster is an interesting poster because it validates something that a lot of us in the field have thought previously, which is, A: the majority of recurrence has happened relatively quickly. And B: when you do supplement the microbiota, it can delay the time to recurrence, meaning that it is still working, but certain patients might need more fortification.