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Clostridioides difficile is a toxin-based infection that takes up residence in the colon due to disturbed normal bowel flora, usually after antibiotics.
Recurrent C. difficile can happen in up to a quarter of patients who receive oral vancomycin as a treatment for their infection. It can also occur with treatment with the newer agent, fidaxomicin, although possibly in fewer patients. In general, relapses are indeed common.
When I trained at Johns Hopkins under John Bartlett, he took the approach that after the second – and always after the third – relapse, an extended course of oral therapy with vancomycin could help get patients out of trouble. He used the so-called extended pulse method, where patients would take the drug for approximately 4-6 weeks and gradually reduce the dose.
This approach can also be done with fidaxomicin. However, I’m not sure it works much better than vancomycin, and there are often hurdles to using fidaxomicin because of insurers not approving it because of the expense.
What other therapies are there?
There is bezlotoxumab, which is a human monoclonal antibody targeting C. difficile toxin B. I’ve used it a few times. It is given as a one-time infusion, and there are challenges regarding cost, the logistics of setting up the infusion, and insurance approval.
Fecal microbiota transplant
In recent years, fecal microbiota transplants (FMT) have received a lot of attention as a different avenue of treatment that could lower the potential for relapses, with success rates usually around 80%-90%. However, in the past few years, there have been some serious safety signals because of possible transmission of dangerous pathogens, often with drug resistance, with FMT.
I’m therefore pleased to say that newer fecal microbiota products are coming in fast and furious. I thought I’d spend a few minutes speaking about these.
OpenBiome, an organization dedicated to microbiome research, offers an investigational product from screened donors that has not received Food and Drug Administration approval. It’s been around for some time. It can be used in either upper or lower GI applications, and the organization cites about an 84% success rate using this product.
There are also two new FDA-approved products I think are worth knowing about. They’ve just been approved recently and we’re a little uncertain of where they’re going to end up in the treatment landscape.
The first is from Ferring, and it goes by fecal microbiota, live-jslm (Rebyota). This is a product from qualified and screened donors, the main component of which is Bacteroides, which is given as a single dose by enema.
The company did a phase 3 trial with a Bayesian primary analysis, which I think convinced the FDA to approve this product. The success rate in people with multiple relapses was 70.6%, compared with 57.5% with placebo. The estimated treatment effect was 13.1%. Of those who did respond, over 90% were kept free of relapse over a 6-month period.
The other product, also FDA approved, is from Seres. It was previously called SER-109, and is now called fecal microbiota spores, live-brpk (Vowst). Unlike the previous product, this is orally administered, with patients taking four capsules daily for 3 days. Again, these donor-derived firmicutes have been appropriately screened and are free of potential pathogens.
The phase 3 randomized clinical trial results were published in the New England Journal of Medicine. They showed that 12% of those taking this product had a relapse, compared with 40% of those taking placebo, which is about the range we tend to see in people who have had multiple relapses. The safety profile was similar to placebo.
So, how will people use these treatments?
I think the FDA imprimatur will be attractive to people, but the products, I believe, will be priced fairly expensively, in the under $10,000 range. The first (Rebyota) is a rectal infusion; it is a one-and-done treatment but creates logistical issues. Interestingly, it could be a billable procedure for infectious disease clinicians. The ease of oral administration for Vowst, no doubt, will be very appealing. Both of these are given after completing a course of treatment with vancomycin or fidaxomicin so as not to interfere with the microbiome product.
I’ll also briefly mention a paper published in JAMA on yet another microbiome product, called VE303. This product was based on eight commensal strains of Clostridia and was given orally in a phase 2 trial. Interestingly, this worked about the same as the oral product that is already FDA approved. The study showed a recurrence rate of 13.8% in the high-dose group, compared with 45.5% in the placebo group.
I think this is exciting. And, of course, there is the expense.
But anything that can be done to help improve these patients is welcome, as once they get into the multiple-relapse phase, it is challenging to turn around. These commercialized products will hopefully become a bit more mainstream. Certainly, we’ll see how these will be utilized in the coming months and over the next few years.
Dr. Auwaerter is Clinical Director, Division of Infectious Diseases, Johns Hopkins University, Baltimore. He reported conflicts of interest with Gilead, Shionogi, and Medscape.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Clostridioides difficile is a toxin-based infection that takes up residence in the colon due to disturbed normal bowel flora, usually after antibiotics.
Recurrent C. difficile can happen in up to a quarter of patients who receive oral vancomycin as a treatment for their infection. It can also occur with treatment with the newer agent, fidaxomicin, although possibly in fewer patients. In general, relapses are indeed common.
When I trained at Johns Hopkins under John Bartlett, he took the approach that after the second – and always after the third – relapse, an extended course of oral therapy with vancomycin could help get patients out of trouble. He used the so-called extended pulse method, where patients would take the drug for approximately 4-6 weeks and gradually reduce the dose.
This approach can also be done with fidaxomicin. However, I’m not sure it works much better than vancomycin, and there are often hurdles to using fidaxomicin because of insurers not approving it because of the expense.
What other therapies are there?
There is bezlotoxumab, which is a human monoclonal antibody targeting C. difficile toxin B. I’ve used it a few times. It is given as a one-time infusion, and there are challenges regarding cost, the logistics of setting up the infusion, and insurance approval.
Fecal microbiota transplant
In recent years, fecal microbiota transplants (FMT) have received a lot of attention as a different avenue of treatment that could lower the potential for relapses, with success rates usually around 80%-90%. However, in the past few years, there have been some serious safety signals because of possible transmission of dangerous pathogens, often with drug resistance, with FMT.
I’m therefore pleased to say that newer fecal microbiota products are coming in fast and furious. I thought I’d spend a few minutes speaking about these.
OpenBiome, an organization dedicated to microbiome research, offers an investigational product from screened donors that has not received Food and Drug Administration approval. It’s been around for some time. It can be used in either upper or lower GI applications, and the organization cites about an 84% success rate using this product.
There are also two new FDA-approved products I think are worth knowing about. They’ve just been approved recently and we’re a little uncertain of where they’re going to end up in the treatment landscape.
The first is from Ferring, and it goes by fecal microbiota, live-jslm (Rebyota). This is a product from qualified and screened donors, the main component of which is Bacteroides, which is given as a single dose by enema.
The company did a phase 3 trial with a Bayesian primary analysis, which I think convinced the FDA to approve this product. The success rate in people with multiple relapses was 70.6%, compared with 57.5% with placebo. The estimated treatment effect was 13.1%. Of those who did respond, over 90% were kept free of relapse over a 6-month period.
The other product, also FDA approved, is from Seres. It was previously called SER-109, and is now called fecal microbiota spores, live-brpk (Vowst). Unlike the previous product, this is orally administered, with patients taking four capsules daily for 3 days. Again, these donor-derived firmicutes have been appropriately screened and are free of potential pathogens.
The phase 3 randomized clinical trial results were published in the New England Journal of Medicine. They showed that 12% of those taking this product had a relapse, compared with 40% of those taking placebo, which is about the range we tend to see in people who have had multiple relapses. The safety profile was similar to placebo.
So, how will people use these treatments?
I think the FDA imprimatur will be attractive to people, but the products, I believe, will be priced fairly expensively, in the under $10,000 range. The first (Rebyota) is a rectal infusion; it is a one-and-done treatment but creates logistical issues. Interestingly, it could be a billable procedure for infectious disease clinicians. The ease of oral administration for Vowst, no doubt, will be very appealing. Both of these are given after completing a course of treatment with vancomycin or fidaxomicin so as not to interfere with the microbiome product.
I’ll also briefly mention a paper published in JAMA on yet another microbiome product, called VE303. This product was based on eight commensal strains of Clostridia and was given orally in a phase 2 trial. Interestingly, this worked about the same as the oral product that is already FDA approved. The study showed a recurrence rate of 13.8% in the high-dose group, compared with 45.5% in the placebo group.
I think this is exciting. And, of course, there is the expense.
But anything that can be done to help improve these patients is welcome, as once they get into the multiple-relapse phase, it is challenging to turn around. These commercialized products will hopefully become a bit more mainstream. Certainly, we’ll see how these will be utilized in the coming months and over the next few years.
Dr. Auwaerter is Clinical Director, Division of Infectious Diseases, Johns Hopkins University, Baltimore. He reported conflicts of interest with Gilead, Shionogi, and Medscape.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Clostridioides difficile is a toxin-based infection that takes up residence in the colon due to disturbed normal bowel flora, usually after antibiotics.
Recurrent C. difficile can happen in up to a quarter of patients who receive oral vancomycin as a treatment for their infection. It can also occur with treatment with the newer agent, fidaxomicin, although possibly in fewer patients. In general, relapses are indeed common.
When I trained at Johns Hopkins under John Bartlett, he took the approach that after the second – and always after the third – relapse, an extended course of oral therapy with vancomycin could help get patients out of trouble. He used the so-called extended pulse method, where patients would take the drug for approximately 4-6 weeks and gradually reduce the dose.
This approach can also be done with fidaxomicin. However, I’m not sure it works much better than vancomycin, and there are often hurdles to using fidaxomicin because of insurers not approving it because of the expense.
What other therapies are there?
There is bezlotoxumab, which is a human monoclonal antibody targeting C. difficile toxin B. I’ve used it a few times. It is given as a one-time infusion, and there are challenges regarding cost, the logistics of setting up the infusion, and insurance approval.
Fecal microbiota transplant
In recent years, fecal microbiota transplants (FMT) have received a lot of attention as a different avenue of treatment that could lower the potential for relapses, with success rates usually around 80%-90%. However, in the past few years, there have been some serious safety signals because of possible transmission of dangerous pathogens, often with drug resistance, with FMT.
I’m therefore pleased to say that newer fecal microbiota products are coming in fast and furious. I thought I’d spend a few minutes speaking about these.
OpenBiome, an organization dedicated to microbiome research, offers an investigational product from screened donors that has not received Food and Drug Administration approval. It’s been around for some time. It can be used in either upper or lower GI applications, and the organization cites about an 84% success rate using this product.
There are also two new FDA-approved products I think are worth knowing about. They’ve just been approved recently and we’re a little uncertain of where they’re going to end up in the treatment landscape.
The first is from Ferring, and it goes by fecal microbiota, live-jslm (Rebyota). This is a product from qualified and screened donors, the main component of which is Bacteroides, which is given as a single dose by enema.
The company did a phase 3 trial with a Bayesian primary analysis, which I think convinced the FDA to approve this product. The success rate in people with multiple relapses was 70.6%, compared with 57.5% with placebo. The estimated treatment effect was 13.1%. Of those who did respond, over 90% were kept free of relapse over a 6-month period.
The other product, also FDA approved, is from Seres. It was previously called SER-109, and is now called fecal microbiota spores, live-brpk (Vowst). Unlike the previous product, this is orally administered, with patients taking four capsules daily for 3 days. Again, these donor-derived firmicutes have been appropriately screened and are free of potential pathogens.
The phase 3 randomized clinical trial results were published in the New England Journal of Medicine. They showed that 12% of those taking this product had a relapse, compared with 40% of those taking placebo, which is about the range we tend to see in people who have had multiple relapses. The safety profile was similar to placebo.
So, how will people use these treatments?
I think the FDA imprimatur will be attractive to people, but the products, I believe, will be priced fairly expensively, in the under $10,000 range. The first (Rebyota) is a rectal infusion; it is a one-and-done treatment but creates logistical issues. Interestingly, it could be a billable procedure for infectious disease clinicians. The ease of oral administration for Vowst, no doubt, will be very appealing. Both of these are given after completing a course of treatment with vancomycin or fidaxomicin so as not to interfere with the microbiome product.
I’ll also briefly mention a paper published in JAMA on yet another microbiome product, called VE303. This product was based on eight commensal strains of Clostridia and was given orally in a phase 2 trial. Interestingly, this worked about the same as the oral product that is already FDA approved. The study showed a recurrence rate of 13.8% in the high-dose group, compared with 45.5% in the placebo group.
I think this is exciting. And, of course, there is the expense.
But anything that can be done to help improve these patients is welcome, as once they get into the multiple-relapse phase, it is challenging to turn around. These commercialized products will hopefully become a bit more mainstream. Certainly, we’ll see how these will be utilized in the coming months and over the next few years.
Dr. Auwaerter is Clinical Director, Division of Infectious Diseases, Johns Hopkins University, Baltimore. He reported conflicts of interest with Gilead, Shionogi, and Medscape.
A version of this article first appeared on Medscape.com.