A new study published online in the journal ClinicalInfectious Diseases looked at the use of a non-frozen capsule of microbiome restoration therapy for treating patients with recurrent C. difficile infection.
“Patients with C. difficile are typically managed with antibiotics or fecal transplantation for recurrent C. difficile,” says the study’s author, Sahil Khanna, M.B.B.S., a gastroenterologist at Mayo Clinic. Dr. Khanna says fecal transplantation has been demonstrated to have high success rates by restoring the gut microbiome of patients. However, he says there are several challenges with fecal transplantation including standardization of the product, keeping it frozen, and mitigating the risk of infectious disease transmission during the procedure.
To help reduce the risks, Dr. Khanna and his team studied a transplantation method using a non-frozen capsule instead of whole stool transplantation. An initial dose-finding, the investigator-initiated study looked at the efficacy of different doses of fecal matter and the safety of performing microbiome restoration therapy using an oral product, RBX7455 developed by Rebiotix, Inc. The team found no concerns related to safety.
“Our study has several implications,” says Dr. Khanna. “We think that products like capsules may be able to replace fecal transplantation that is currently done via a colonoscopy. We also think that products that are non-frozen may allow for repeat dosing and for patient-administered self-treatment at home. The good news is that we are moving closer to having safe and effective products to restore the gut microbiome for patients with recurrent C. difficile.”
Dr. Khanna says that larger clinical trials and blinded, placebo-controlled trials are the next step in moving this potential treatment from research into practice.
Click on the graphic above to access the World Microbiome 2020 Page
World Microbiome Day was founded by APC Microbiome Ireland in 2019. It aims to celebrate all things microbe and to raise awareness of the diverse world of microbiomes and their impact on human, animal, and environmental health.
In honour of the World Microbiome Day 2020 day, the BMC is proud to present this collection of microbiome research specially selected by our editors.
The BMC (Biomed Central) Research In Progress — A pioneer of open access publishing, BMC has an evolving portfolio of high quality peer-reviewed journals including broad interest titles such as BMC Biology and BMC Medicine, specialist journals such as Malaria Journal and Microbiome, and the BMC Series.
Expanding beyond biomedicine into the physical sciences, mathematics and engineering disciplines, BMC now offers a wider portfolio of subject fields on a single open access platform.
At BMC, research is always in progress. We are committed to continual innovation to better support the needs of our communities, ensuring the integrity of the research we publish, and championing the benefits of open research. BMC is part of Springer Nature.
BMC has an evolving portfolio of some 300 peer-reviewed journals, sharing discoveries from research communities in science, technology, engineering and medicine. In 1999 we made high quality research open to everyone who needed to access it – and in making the open access model sustainable, we changed the world of academic publishing.
Microbiota Restoration in Recurrent C. difficile (C. diff. ) and COVID-19
This activity is intended for gastroenterologists, infectious disease specialists, and other clinicians who care for patients at risk of serious infection.
Activity Purpose: While the incidence of multiply recurrent C. difficile continues to rise, FMT has emerged as a means to break the cycle. Amid the current COVID-19 pandemic, clinicians should be aware of the additional safety concerns that have arisen. Expert faculty will discuss approaches to FMT including sourcing and screening of donor stool, which requires heightened safety measures during the COVID-19 pandemic. This activity is the first in a series of two educational activities that address the latest data on treating patients who experience rCDI.
Please click on the following link to be redirected to the activity
This is a promising approach to managing CDI. Completion of a Phase 3 study, with positive results, is exciting and holds much promise for patients suffering with recurrent C. diff. infections.
We look forward to the final results and are truly grateful.
Rebiotix and Ferring announce world’s first with positive preliminary pivotal Phase 3 data for investigational microbiome-based therapy RBX2660
Rebiotix and Ferring are the first to announce positive preliminary results on primary
efficacy endpoint from ongoing pivotal Phase 3 clinical trial for RBX2660
RBX2660 is an investigational, non-antibiotic, microbiome-based therapy, developed to
reduce Clostridiodes difficile (C. diff) infection recurrences
The CDC defines C. diff as a major burden to patients and doctors and an urgent healthcare
threat causing an estimated half a million illnesses and thousands of deaths annually in the
US alone ( 1 , 2)
Source: Press Release
Roseville, Minnesota and Saint-Prex, Switzerland – 6 May, 2020, 07:00 EST –
Today, . These preliminary positive efficacy findings mark an important milestone, advancing RBX2660 in its clinical development program with a goal of bringing a US FDA approved therapy to patients. The clinical development program for RBX2660 is the most advanced in the world in evaluating the safety and efficacy of a standardized, non-antibiotic microbiome-based therapy.
RBX2660 is being developed to reduce C. diffinfection recurrences, an urgent unmet need for
patients and healthcare providers worldwide. Antibiotics, the current standard of care, have been shown to disrupt the microbiome and increase the risk of C. diff recurrence. 3
C. diff causes nearly 30,000 deaths each year in the US; in Europe, the incidence of C. diff is increasing, with recurrent bouts of infection representing 10-15% of all healthcare-related infections in hospitals annually. 4 , 5
As a live biotherapeutic, aiming to help restore the gut microbiome community, RBX2660 may bring an innovative therapeutic option to patients suffering from this potentially deadly infection. “C. diff infection is a significant public health threat that has limited treatment options. These positive preliminary findings represent a major step forward towards bringing an innovative, non-antibiotic option to patients that may help restore their gut microbiome, said Per Falk, Ferring’s President and Chief Science Officer. With health systems under increasing pressure due to viruses like COVID-19 and the rising threat of antimicrobial resistance, the need for new therapies is greater than ever. We believe the power of the microbiome has great potential and we look forward to bringing RBX2660 to patients soon.”
“Since founding Rebiotix in 2011, our mission has been to harness the power of the microbiome to treat complex diseases. Our first goal was to address C. diff, which poses a significant health threat to thousands worldwide every year,” said Lee Jones, CEO and founder of Rebiotix, a Ferring company.
The positive preliminary data on the primary efficacy endpoint are a major stepping stone
for the RBX2660 development program, bringing us closer to an approved microbiome therapy
available for healthcare providers to help patients. As a first-in-class, potentially paradigm-changing technology, we look forward to discussing our final data with the FDA in the latter part of this year.” The ongoing Phase 3 trial is a randomized, multicenter, double-blinded, placebo-controlled study. The trial also incorporates a safety assessment intended to follow patients for several months after receiving the investigational drug. The safety data will provide insight into the potential of using microbes as a therapeutic intervention. The full data package is anticipated in the second half of 2020.
This trial builds on nearly a decade of research and evaluation of the formulation, with robust clinicaland microbiome data collected over multiple controlled trials under the proprietary MRT drug platform.
About Clostridioides difficile infection (C. diff)
C. diff is a bacterium that causes diarrhea and colitis (an inflammation of the colon). 6 It is estimated to cause up to half a million illnesses in the US alone every year and is considered an urgent threat to public health by the CDC, and can lead to severe complications, including hospitalization, surgery, and death. 2 While antibiotics are the standard of care to address the infection, they are also the primary risk factor for disease recurrence. 3 Recurrence of C. diff occurs in approximately 15- 50% of patients. 7
About the microbiome
The human microbiome is a complex community of microorganisms which live on every surface of the body. The microbiome aids in the maintenance and development of the immune system,
metabolism, and other functions essential to human life. 8 The gastrointestinal tract houses the most dense and complex population of microbiota, which has an incredible influence over daily health – from aiding in food digestion to fighting disease. Clinical and scientific studies indicate antibiotics, viruses, stress and other factors can disturb the gut microbiota. This disruption, often referred to as “dysbiosis,” may have negative health impacts, and promote conditions for infections like C. dif infection to take hold. 9
Rebiotix and Ferring believe there is tremendous potential in microbiota-based therapies to address such illnesses, and are evaluating this therapeutic option through their
pioneering microbiota-based MRT drug platform, beginning with recurrent C. diff infection.
The investigational RBX2660 formulation is the first-in-class microbiota-based therapy to achieve positive preliminary Phase 3 study results. RBX2660 is being developed to help break the cycle of recurrent C. diff infection. The therapy has been granted Fast Track, Orphan, and Breakthrough Therapy designations from the US FDA. The RBX2660 ongoing pivotal Phase 3 trial, PUNCH CD3, is a randomized, multicenter, double-blinded, placebo-controlled study. For more information about the RBX2660 Phase 3 study, visit http://www.clinicaltrials.gov (NCT03244644).
About Ferring Pharmaceutical Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. Headquartered in Saint-Prex,Switzerland, Ferring is a leader in reproductive medicine and maternal health, and in specialty areas within gastroenterology and urology. Founded in 1950, privately-owned Ferring now employs approximately 6,500 people worldwide, has its own operating subsidiaries in nearly 60 countries and markets its products in 110 countries.Learn more at http://www.ferring.com, or connect with us on Twitter, Facebook, Instagram, LinkedIn and YouTube.
Rebiotix Inc, part of the Ferring Pharmaceuticals Group, is a late-stage clinical microbiome
company focused on harnessing the power of the human microbiome to revolutionize the treatment of challenging diseases. Rebiotix has a diverse pipeline of investigational drug products built on its pioneering microbiota-based MRT drug platform. The platform consists of investigational drug technologies designed to potentially rehabilitate the human microbiome by delivering a broad consortium of live microbes into a patient’s intestinal tract. For more information on Rebiotix and its pipeline of human microbiome-directed therapies for diverse disease states, visit http://www.rebiotix.com, or connect with us on Twitter, Facebook, LinkedIn and YouTube.
For more information, please contact
Rebiotix Inc., a Ferring Company
+1 651 705 8774 (direct)
1 Centers for Disease Control and Prevention. What Is C. Diff?17 Dec. 2018. Available at: https://www.cdc.gov/cdiff/what-is.html.
2 Centers for Disease Control and Prevention. Biggest Threats and Data, 14 Nov. 2019. Available at: https://www.cdc.gov/drugresistance/biggest-threats.html.
3 Theriot CM, Young VB. Microbial and metabolic interactions between the gastrointestinal tract and
Clostridium difficile infection. Gut Microbes. 2013;5(1):86-95. doi:10.4161/gmic.27131.
4 Lessa FC, Mu Y, Bamberg WM, et al., Burden of Clostridium difficile Infection in the United States. New
England Journal of Medicine. 2015;372(9):825-834. doi:10.1056/nejmoa1408913.
5 DRG Report 2016 Clostridium Difficile.
6 Centers for Disease Control and Prevention. Clostridiodes difficile Fact Sheet. Available at:
7 Stevens VW, Nelson RE, Schwab-Daugherty EM, et al., Comparative Effectiveness of Vancomycin and
Metronidazole for the Prevention of Recurrence and Death in Patients with Clostridium difficile Infection.
JAMA Intern Med. 2017;177(4):546–553. doi:10.1001/jamainternmed.2016.9045.
8 Mohajeri MH, Brummer RJM, Rastall RA, et al., The role of the microbiome for human health: from basic
science to clinical applications. Eur J Nutr. 2018;57(Suppl 1):1–14. doi:10.1007/s00394-018-1703-4.
9 Quigley EM. Gut bacteria in health and disease. Gastroenterol Hepatol (N Y). 2013;9(9):560–569.
It has access to the largest surface area of the body, alters drugs before they even enter the blood stream and could be a potent medicinal weapon… yet there is much we still don’t understand about the microbiome.
Here David Kirk and Ben Bradley tell us about their attempts to heal us from within
We are not alone. We are inhabited by hundreds of species of microbes, which represent millions of genes. Together, these microscopic organisms – bacteria, fungi, archaea and viruses – and their collective genomes make up the microbiome.
To review this article in its entirety please click on the following link:
In the gut, microbes break down otherwise indigestible dietary fibres and release nutrients, such as B-vitamins and short chain fatty acids, which can be absorbed by the intestines. They secrete other small molecules or peptides which interact with the body via the bloodstream and immune system. The majority of these have yet to be identified and characterised. In addition, commensal microbes deter opportunistic pathogens from invading the competitive niche of the intestinal tract.
LBPs are a recent concept and have their origins in a novel treatment for C. difficile infection: the faecal microbiota transplant… this is exactly what you think it is
The disruption of the microbiome, termed dysbiosis, is associated with an ever-growing list of conditions. Obesity and metabolic syndrome, for instance, are associated with a microbiome less diverse than that of a healthy individual. Inflammatory bowel disease (IBD) and colorectal cancer are associated with a decrease in butyrate-producing bacteria like Clostridia, and an increase in Enterobacteriaceae and Bacilli.
An air of scepticism comes with the phrase “associated”. Microbiome research is still a developing field, and the presence or absence of a single species or genus cannot be directly blamed for conditions like obesity or IBD in all patients. The complex interplay between host and microbiome depends as much on the host’s genetic susceptibility and environment as on the dysbiosis or lack of diversity in the microbiome. The million dollar question remains: What exactly constitutes a ‘healthy microbiome’?
A powerful tool
The microbiome is adaptive and changes in response to diet, environment and disease. It has become increasingly clear that many drugs interact with the microbiome, with some requiring microbiota derived enzymes for activation and others being rendered non-functional or even toxic via microbiota dependant conversion. As research in host-microbe interaction continues, more accurate relationships between the microbiome and human illness will be uncovered.
The gut microbiome presents an interesting medicinal target in itself. It interacts directly with one of the largest surface areas of the body. Therefore it has easy access to the bloodstream through diffusion of nutrients and small molecules, and via a mucosal layer rich in multiple cell types of the adaptive and innate immune systems. Due to the powerful delivering capacity of the gut, most microbial-based treatments in development aim to add to the microbiome rather than take away from it.
Microbial therapies using living organisms are known as live biotherapeutic products (LBPs). LBPs are a recent concept and have their origins in a novel treatment for C. difficile infection (CDI): the faecal microbiota transplant.
This is exactly what you think it is.
CDI occurs when the gut microbiome is wiped out by antibiotic use and becomes infected by C. difficile, an organism that is normally unable to compete against the natural microbiota. This illness may recur in spite of further antibiotic treatments, and can be fatal. The most effective treatment, in extreme cases, is a faecal transplant into the infected recipient. Transplanted microbes thrive and outcompete C. difficile, effectively reversing the infection in over 90% of cases. But due to the uncertainty of what constitutes a ‘healthy microbiome’, a faecal transplant cannot be considered a cure-all for dysbiosis-associated illness.
Daunting clinical trials
This “unknown” of host-microbe interaction sparked the need to develop defined microbiome therapies. Naturally, CDI was one of the first targets for a defined treatment. Several companies are developing and trialling defined cocktails of bacteria known to safely inhabit the gut with the goal of outcompeting C. difficile with Seres Therapeutics and Rebiotix entering phase 3 trials in 2018.
CHAIN Biotech is developing technology to deliver therapeutics to the gut microbiome using engineered Clostridium, a spore forming bacterium, and have a lead candidate targeting IBD. IBD is a collection of inflammatory diseases of the gut, commonly treated with steroid injections which cause numerous unpleasant side effects. Our approach is to deliver an LBP directly to the gut, where it can produce an anti-inflammatory in situ. We also make use of this species’ natural ability to produce spores, which survive the acidic environment of the stomach and germinates into therapeutic-producing cells only in the anaerobic environment of the lower intestine.
This elementary approach – adding one organism with a safe history of use in the human gut, and having it produce one novel product – minimizes the risk of disruption to the microbiome and delivers the treatment directly to the affected area. The next stages, taking LBPs to clinical trial, are daunting. A lot of unknowns exist around the human gut microbiome and these kinds of treatments. Few microbiome companies have LBPs in late-stage clinical trial, but those that do give hope to both patients and us that LBPs will someday heal us from within.