An interview with the Rebiotix founder on the microbiota-based therapy and the newest preliminary pivotal phase 3 findings.
Preliminary findings from an ongoing pivotal phase 3 trial show clinical benefit for investigative microbiome-based therapy RBX2660 for patients with Clostridioides difficile (C diff).
The formulation, from Rebiotix and Ferring Pharmaceuticals, is now the first-in-class microbiota-based therapy to report even preliminary positive phase 3 results for C diff.
Investigators are currently assessing RBX2660 over several months in a randomized, multicenter, double-blinded, placebo-controlled study which incorporates safety outcomes. It builds on a decade of previous research and findings into the therapy’s role in clinical and microbiome treatment, and will be made fully available in the latter half of 2020.
RBX2660 is being developed to help break the cycle of recurrent C diff infection, and has already been granted US Food and Drug Administration (FDA) Fast Track, Orphan, and Breakthrough Therapy designations prior to marketing decision.
In an interview with Contagion® regarding RBX2660 and the most recent findings, Rebiotix chief executive officer and founder Lee Jones discussed the development of the therapy, the newest preliminary phase 3 data, and the role of the microbiome in treating the burdened, recurrent C diff patient population.
Contagion: How are these findings going to influence care in C. difficile?
Jones: From the beginning, when I found Rebiotix back in 2011, our goal was to use the microbiome to treat diseases. And as you know, C diff is one of those unmet medical needs where it seemed like a microbial therapy would work. So, we've spent the last 8 years doing multiple clinical studies to demonstrate that this actually is a viable therapy for people who don't have any options, or where antibiotics maybe don't work for them.
So, it's not only exciting for the patient standpoint—because we've waited a long time to bring something like this out to them—but also from a microbiome industry standpoint. It gives us an opportunity to say, 'See, it can be done,' since this is the first product to actually make it through and have a successful phase 3 trial. We believe this gives a good indication to others that this is a real therapeutic opportunity, and that this may hopefully increase investment in the area.
Contagion: What are the big takeaways in the jump from phase 2 to phase 3 findings?
Jones: I think this has been an incredibly difficult time to be able to bring this type of data forward. As we started doing our work early in 2012, we had to learn a lot about this patient population and start developing the whole clinical infrastructure. It wasn't a simple, straightforward, typical clinical program. It was made more complicated with the fact that the FDA had allowed for enforcement discretion.
Other companies that were stool-based started to selling products in this arena. So, gathering this data and demonstrating that we can have a safe and efficacious treatment for recurrent C diff, and documenting that with these multiple clinical trials is a major, major milestone. I think getting to phase 3—and then having a successful phase 3 trial—is really important, not only for our own development, but also to bring this therapy forward.
Contagion: The future burden of hospital care is something that's yet to be dictated due to the coronavirus 2019 (COVID-19) pandemic, but it will likely change over time. Can you speak to the benefit of added therapeutic options for hospital-based diseases such as C diff?
Jones: We think that with COVID-19 and all the people that are ending up in the ICU, we're going to see a large bloom in C diff patients going forward. So, I think trying to keep those people out of the hospitals, so that they're not posing a further healthcare burden and giving them an option that's not antibiotic, we're giving them the opportunity to essentially treat their own disease.
And it makes such a huge difference, because if this is successful, it's possible to treat this without antibiotic therapies. And that will preserve our antibiotic legacy going forward in time.
Contagion: How has clinical research into RBX2660 influenced your team's understanding of the gut microbiome?
Jones: When we first got started, we started collecting patient samples from all of our clinical study subjects. We've conducted now 5 clinical studies and have followed several hundred people for over 2 years.
We continue to capture fecal samples over that time period. What that allowed us to do is the generate a huge biorepository of longitudinal samples so we can track what happens to the microbiome prior to treatment, post-treatment and then over long periods of time—even if they undergo other treatments for other diseases—to see what it looks like, what diseases it impacts.
And we're finding it's a great set of data to start building off of to look for other indications and other diseases.
Contagion: C diff is obviously a burdensome disease for patients, but its mortality risk may also be underestimated among the population. How does it affect patients who are being treated in this trial?
Jones: I think that's the thing that's the most heartbreaking. C diff is a disease that's often hidden, because people end up with multiple episodes of diarrhea, which means they're trapped at home. They don't get to go out to the store, their quality of life is horrible. Students that are in college often have to drop out, people can't go back to work.
But because there's nobody out there shouting and pointing at their house and saying, 'Hey, my mom's trapped in there,' you don't hear much about it unless you happen to be in the industry.
What's happened is that because of microbiome therapies and the fact that the CDC declared C diff as an urgent national threat, there's been a lot more activity and more education around C. diff. And what that's done is allowed people to come out of the woodwork and patient advocate groups to arise—along with an understanding that antibiotics do create a situation where people are more susceptible to C. diff.
So, when we have a microbiome therapy, like we're talking about, and we can restore the gut microbiome and take away the opportunity for them to have another episode, it gives them their life back.
And it's been interesting for us, because my own family has suffered from C diff and recurrent C diff. But I didn't know what it was at the time—I just heard it was a diarrheal disease. And as we got into this, I realized they had what exactly I'm trying to prevent in other people.
We've not only seen people have their lives back so that they feel totally differently, but other diseases that they might have had seem to get better, too. So overall, we believe that we're really providing a good therapy for these people, and expect to be able to do this more in the future.
Contagion: What comes next, in terms of data presentation?
Jones: Right now, we only have a very minimal data set—mostly that says we achieved our primary endpoint, and that it's statistically significant. The data is still blinded, and the follow-up is still ongoing, so until we're able to lock the database and really analyze the patient population, we don't have a data to share. But we expect at that point in time, we would be doing more about what the actual data says.
Contagion: How are hopes for eventual FDA approval?
Jones: We're pretty bullish on that. This was the final piece of information we needed to be able to move forward with our biologic license application (BLA). So, depending on what happens with the world—if the FDA can get back into their offices and things can move on a more normal pace—we expect, hopefully, an approval sometime next year.
But in the meantime, our goal is to continue to investigate these products for C diff and other indications. We're really excited. We believe that this actually shows the industry that this can be done and gives hope to a lot of people that there are new therapies coming out for people that don't have any other options.