Investigative C. Diff Treatment Shows Success in Patients With Underlying Comorbidities

Pharmacy Times spoke with Paul Feuerstadt, MD, FACG, AGAF, about the investigative C. difficile treatment RBX2660. Recent research investigated its efficacy in patients with underlying comorbidities.

Q: What underlying comorbidities can affect patients with C. diff?

Paul Feuerstadt, MD, FACG, AGAF: So, there's a lot of comorbidities that can impact patients with C. diff. Really what you're asking me is what are the risk factors for recurrence, and I like to group these into several different categories: demographics, medication, exposures, environment, and bacterial virulence factors. From a demographical standpoint, age over 65, any form of immune compromise (chronic kidney disease, HIV, inflammatory bowel disease, diabetes), any distant history of C. difficile can play a role. Medication wise, antimicrobials are a big player, amoxicillin, ampicillin, clarithromycin, fluoroquinolones, cephalosporins, piperacillin tazobactam. As a gastroenterologist, I of course have to include proton pump inhibitors, because they always show up as a risk factor for initial infection and your risk factor for recurrence. We believe it's actually a result of alterations to the microbiota. When we think about bacterial virulence factors, we think about the NAP1/B1/027 strain or the hypervirulent strains, as well as whether the patients have severe infection defined by a white cell count greater than 15,000 and creatinine greater than 1.5 milligrams per deciliter. And finally, the environment that the patient is coming from, do they live in a skilled nursing facility? Are they in the hospital frequently, because if they are, they probably have a lot of the other risk factors. But also, they're surrounded by people who potentially have C. difficile.

So, when we contextualize this information, it's important to understand who's at greatest risk for recurrence. And what this abstract did was it looked at something called the Charlson Comorbidity Score, which is a scoring system for underlying comorbidities. And within this study, patients were grouped into 1 of 3 groups: mild Charlson comorbidity score, which is a score of 0 to 2; moderate score of 3 to 4; and severe, greater than 5. And using this breakdown, we carved up the specific PUNCH CD3 cohort of 262 total patients, and 107 of them had mild disease, 71 had moderate, and 84 had severe. And then we looked at the efficacy of RBX2660 within those subgroups, different than the subgroups from the other abstract.

And what they found was very consistent efficacy. Efficacy was 76.5% in the mild group, efficacy was 68.0% in the moderate, and 67.8% in the severe. So, we see trends for greater efficacy than placebo in all 3 groups. Importantly, in the mild group, as you would expect, as a younger group, you have a greater efficacy at 8 weeks than the moderate and severe. Interestingly enough, there were very similar treatment effects—68.0, 67.8%. That is despite the placebo effect, the placebo treatment being lower efficacy in the severe cohort than the moderate cohort. So, what we're seeing is RBX2660 really being consistently efficacious, but having a very profound effect in the moderate and severe cohort, again, speaking to the fact that this is a product that can be used after standard of care antimicrobial in a broad range of patients and still have very good effects.

Are there gaps in care for these patients?

Paul Feuerstadt, MD, FACG, AGAF: So, without RBX2660, they're facing being treated only partially, right? As we discussed, RBX2660 as a supplement to the microbiota, what we're currently using are antimicrobials. And then if you have the opportunity to go to a coronary care center where fecal microbiota transplantation is performed under enforcement discretion through the FDA, you might be able to get that second piece to shut down the cycle of recurrence, but the majority of patients don't have access to that. Thus, they're really only being treated with the standard of care antimicrobials, and it's up to their own microbiota to regrow and that leaves these patients prone to that 35% initial recurrence rate. And up to 65% of those with 2 or more recurrences getting stuck in the cycle of recurrence after recurrence after occurrence.

Q: Can you discuss the safety profile and adverse effects for RBX2660?

Paul Feuerstadt, MD, FACG, AGAF: You know, that's a really important question. Safety signals with regards to RBX2660 have been on par with what one might expect and they're really minor. The majority of patients that have side effects from this are usually gas, bloating, or changes in bowel habits. They're usually short lived, and they're classified as minor. Lindy Banky presented a very nice abstracted at ID Week back in the Fall of 2021 that looked at the 3 phase 2 trials and the 2 phase 3 trials considering RBX2660, and showed very consistent safety for these products and in a separate abstract consistent efficacy. So, we see that the safety profile for RBX2660 is very encouraging as well.

Q: Is there anything you want to add?

Paul Feuerstadt, MD, FACG, AGAF: You know, I think I'm just going to add something in general. You know the Charlson comorbidity poste, and the subgroup analysis shows broad applicability of this product. The recurrence data shows again broad applicability of this product consistent with what many hypothesize with microbiota-based live biotherapeutics. I think it's just so important to understand that RBX2660 and microbiota-based live biotherapeutics are the future, they are going to be a piece of how we treat C. difficile infection, and specifically recurrent C. difficile infection. And we're really seeing the light at the end of the tunnel. We're seeing, hopefully, an FDA-approved product within the next 12 months. And if that happens, this will give so much better access to so many more patients of treatments that they need to shut down that cycle to decrease morbidity, to decrease mortality, to improve patients’ quality of life. So, as a clinician, it's just so exciting for me to see the potential for broad applicability of technology that I've had access to for a long time with foundational fecal microbiota transplants. But now, having phase 2, phase 3 data that's consistent in a broad range of patients, that's incredibly exciting for patients and for clinicians.