Category Archives: C.diff. in the news

Rebiotix and Ferring Pharmaceuticals Announced Positive Preliminary Findings From Their Ongoing Pivotal Phase 3 Trial Of the Investigational Microbiome-based Treatment RBX2660

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. diff infection 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.

About RBX2660

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.

About Rebiotix
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
Courtney Jones
Marketing Manager
Rebiotix Inc., a Ferring Company
+1 651 705 8774 (direct)
courtney.jones@ferring.com

Lindsey Rodger
Senior Manager, Corporate Communications
Ferring Pharmaceuticals
+41 58 451 4023 (direct)
+41 79 191 0486 (mobile)
lindsey.rodger@ferring.com

References
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:

Click to access Cdiff-Factsheet-P.pdf


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.

Merck and Premier Applied Sciences Will Develop Software To Provide C.difficile Infection Education and Provide Surveillance

Merck & Co is working a major US hospital provider on a new software system that could help tackle the threat from healthcare-associated infections, the leading HAI:   C. diff.  infections.

 

 

 

The pharma company’s deal with Premier will see the partners develop and test the combination of a software-based platform and a coordinator to provide surveillance, consultation, support and education to patients with Clostridium difficile infection (C. diff).

Sam Bozzette, MD, chief scientist of Premier’s retrospective and interventional research division Premier Applied Sciences, said: “By increasing clinician and patient knowledge of this often prolonged, and sometimes deadly infection, and developing and testing a software-based application to help reduce the recurrence of C. diff. infection by improving follow-up and management, we believe there is a strong potential to make a real difference to address this critical public health problem.”

Sam Bozzette, MD, PhD, vice president and chief scientist of its retrospective and interventional research division, Premier Applied Sciences.  An internationally-recognized researcher and physician executive, Dr. Bozzette provides strategic clinical, analytical and operational direction to further grow the Premier Applied Sciences research business and improve the overall quality, safety and cost-effectiveness of care.  “Dr. Bozzette is a leader in medical and social sciences, and has more than 25 years of experience working with academic and non-profit healthcare providers to improve clinical decision-making practices, care delivery efficiency and effectiveness, and population health management,” said Leigh Anderson, chief information officer at Premier. “We are thrilled to have him on board to lead Premier’s data-driven research efforts to set new standards in care delivery through strategic partnerships with healthcare industry leaders across the U.S.”

Premier Applied Sciences, formerly known as Premier Research Services, combines data and analytics with objective clinical outcomes analyses, and partnerships with health systems, life sciences companies, academic institutions and professional societies to develop, teach, test and research care delivery practices and real-world interventions for healthcare improvement. It offers real-world research and analytics, retrospective research, healthcare education, clinical trial innovation and data licensing services.

Resources:  https://pharmaphorum.com/news/merck-co-software-c-diff-infections/

https://www.premierinc.com/dr-sam-bozzette-joins-premier-inc-lead-research-division/

The work expands Merck’s chronic disease work with Premier, which has seen them co-develop and test solutions that help promote wellness and prevention for specific groups of at-risk patients since 2016.

Raquel Tapia, associate VP, hospital/specialty marketing at Merck, said: “Combining the technical capabilities of Premier and the therapeutic area expertise of Merck has been instrumental in our ability to address these difficult healthcare challenges.

“By testing the solutions in real-world settings and learning from our growing knowledge base, we’re confident that our work together will help patients.”

The partners’ goal is to increase patient access to healthcare services, raise awareness of how to decrease patient risk of recurrence and help patients identify if they are having a recurrence.

The proposed C. diff software intervention will be tested within volunteer Premier member health systems. The firm current has an alliance of around 3,900 US hospitals and health systems and a further 150,000 or so healthcare providers and organizations.

C. diff infections cause serious and life-threatening diarrhea and have become one of the most common microbial cause of healthcare-associated infections in US hospitals. It’s thought that C. diff infections affect approximately half a million people and add $4.8 billion to US healthcare costs each year.

Clostridium difficile in Scotland Have Increased Significantly

Cases of the potentially deadly hospital infection Clostridium difficile in Scotland have increased significantly, figures show. Between April and June, 322 cases of the bug were diagnosed in patients over 65, compared to 270 the previous quarter, Health Protection Scotland (HPS) said the increasing rate was “statistically significant” and in the case of NHS Lothian, specialist support was being given to bring infections down. But the HPS report also found that cases of MRSA had fallen to the lowest ever recorded, with just 27 cases between April and June.

On the issue of C difficile, cases were shown to rising in both older and younger patients. The figures revealed there were 100 new C difficile cases in patients aged 15 to 64 years, compared to 92 the previous quarter. How to Support the ‘Night Owl’ Remote Worker Sponsored by Microsoft 365 [Opt out of Adyoulike ad targeting] HPS said rates for over-65s in NHS Lothian were higher than expected and extra support was being given to tackle the issue. “During this period, NHS Lothian reported an increased incidence of C difficile infection (CDI) to HPS,” the agency said. “HPS are providing on-going support to NHS Lothian in order reduce CDI in the board.” It said no other boards had rates which meant they were a cause for concern in the last quarter. The increasing rate of C difficile in Scotland in the most recent release follow previous reports showing infections falling to record lows following greater efforts to combat bugs and improve hospital cleanliness.

Health Secretary Alex Neil said: “Tackling healthcare associated infections is one of this government’s key priorities and Scotland is widely recognised across the globe as having some of the safest hospitals in the world. “This co-ordinated effort across Scotland’s NHS has had a significant impact on infection rates, with cases of MRSA having reduced by 89.2 per cent and cases of C difficule by 81.9 per cent since national monitoring began. “This quarter we saw cases of MRSA at their lowest levels on record and similarly last quarter C difficile cases were also at their lowest level. “So while we’ve seen increases in the number of cases of                C difficile and MSSA between April and June this year, this should be seen in the context of the dramatic fall in infection rates that have been achieved over the last few years. “

But even these relatively small fluctuations should serve as a clear indication that we must not let up in our drive to tackle this issue. “That is why, working with our key partners, we will continue to monitor infection rates and hospital cleanliness and act immediately where necessary to minimise healthcare associated infections.” The figures comes just over five years since a public inquiry into a deadly outbreak of C difficile at the Vale of Leven Hospital in Dunbartonshire first started, but which has yet to report its findings following a series of delays. Fiona Cameron, Head of Service Infection Prevention & Control, NHS Lothian, said: “NHS Lothian has experienced an increase in the number of cases of Clostridium difficile and we have drafted a robust action plan to identify and eradicate the cause. “As part of that action plan we recently recruited additional infection and prevention control nurses, increased education and ward rounds and began reviewing policies and guidance in relation to the prescription of antibiotic medicine, which is known to be related to Clostridium difficile.

“We have also asked Health Protection Scotland (HPS) to support our work and review our actions to provide any additional input and review actions so far.”

 

Read more at: http://www.scotsman.com/news/cases-of-fatal-hospital-infection-c-difficile-up-1-3561251

Researchers From Loyola Medicine Retrospectively Studied 100 Vancomycin Taper and Pulse Treatment Patients Treated For Recurrent C. difficile Infection

A tapered and pulsed regimen with vancomycin — with diligent follow-up — can achieve significant cure rates in recurrent Clostridium difficile (C. difficile) infected patients, according to a new study.

Researchers from Loyola Medicine retrospectively studied 100 vancomycin taper and pulse treatment patients treated for recurrent C. difficile infection between January 1, 2009 and December 31, 2014. Their clinic, the study authors wrote, has been a referral center for the infection for the past decade.

To read the article in its entirety please click on the following link:

http://www.mdmag.com/medical-news/pulsed-and-tapered-vancomycin-likely-route-to-recurrent-clostridium-difficile-cure

However, despite the guidelines for treatment of recurrent C. difficile infection being not too different than recurrent episodes – except for the use of vancomycin when the case is severe – there have not been many studies on this vancomycin taper and pulsed dosing. 

The researchers observed that after a referral, the confirmed recurrent C. difficile patients were treated with a vancomycin taper and pulse regimen: a taper of vancomycin to once-daily, followed by alternate day dosing; or once-daily followed by alternate day dosing; followed by every third day, for at least 2 weeks. After this regimen, all patients had 90-day follow-up documentation.

On average, the patients in the clinic were on their third C. difficile diarrhea episode. Half of the patients had also received a standard course of vancomycin, while another third had received some type of vancomycin taper regimen, the researchers said.

Despite the fact that many of these patients were a “treatment experienced” population, 75% of the patients who received a supervised vancomycin taper and pulsed regimen achieved a cure,  study author Stuart Johnson  MD, . He added that the results were further improved for patients who received the expended pulse phase: 81% achieved a cure.

“The findings were not unexpected to us, but I think that many clinicians will be surprised how well a deliberate, prolonged vancomycin taper and pulse regimen – with careful follow up – works,” Johnson said.

There were no significant differences among the patients in terms of gender, age, concomitant antibiotics, proton pump inhibitor use, histamine receptor-2 blocker use, or patients with a regimen greater than 10 weeks in length, the researchers continued.

The researchers added that their finding of improved cure rates with alternate-day dosing plus every third day dosing over strictly alternate-day dosing is consistent with the hypothesis that pulsed dosing can promote a cyclical decrease in spore burden, they wrote. This can also permit the resetting of normal microbiota in the gut.

Johnson concluded that the clinical implications of the study show most recurrent C. difficile patients do not need fecal microbiota transplant (FMT).

“FMT has received an enormous amount of press and this procedure is now widely available throughout the US,” Johnson said. “FMT is attractive because it addresses one of the primary mechanisms involved with recurrent C. difficile infection, a marked disruption of the resident bacteria that populate the intestine and provide an important host defense against C. difficile.

Although physicians screen donor feces for “known pathogens,” not all is known of the potential complications to come from FMT, Johnson said.

“In addition, it appears that efficacy with a carefully supervised vancomycin taper and pulse regimen compare to that achieved with FMT,” Johnson said.

The study, “Vancomycin Taper and Pulsed Regimen with careful Follow up for Patients with Recurrent Clostridium difficile Infection,” was published in the journal Clinical Infectious Diseases.

C. diff. May Carry Risks in Preoperative and Postoperative Patients

 

There are risks for acquiring a C. difficile infection (CDI).

The risks range from the overuse of Antibiotics, Immunosuppressed patients, prolonged hospital stays, being a patient in a long-term care facility, and for the senior population.

There may also be a risk for the surgical patients and the following study explains the study and the results:

To read the article in its entirety please click on the following link: https://cdifffoundation.wordpress.com/wp-admin/post-new.php

A lengthy study of four surgical specialties has determined that Clostridium difficile infection (CDI) is a major risk factor for postoperative patients, although incidences varied.

Although it has been shown that CDI is associated with increased cost, morbidity and mortality in patients after surgery, this is the first to examine C. difficile rates across multiple surgical specialties (Infect Control Hosp Epidemiol 2017:1-4. doi: 10.1017/ice.2017.158).

“This study has great importance as the landscape of repayment for elective surgical procedures changes,” said the study’s lead author, James Bernatz, MD, a surgeon with the Department of Orthopedics and Rehabilitative Medicine at University of Wisconsin Hospital and Clinics, in Madison. “With more surgeries being reimbursed as bundled payments, hospitals are pressured to limit costs. As C. diff infection has been found to increase length of stay by one week and double the cost of care, it is clearly a postoperative complication to be avoided.”

Dr. Bernatz and his colleagues conducted the study at a 592-bed tertiary care academic center. They used the hospital’s quality improvement database to review admissions to the orthopedic surgery, neurosurgery, trauma surgery and general surgery units from January 2014 through July 2016. Those patients who underwent an inpatient surgical procedure, and did not meet the exclusion criteria, were surveyed.

Case patients were defined as those who underwent an inpatient procedure and subsequently developed a health care–associated CDI, which was defined as a positive polymerase chain reaction (PCR) test result for C. difficile toxin gene recorded more than 72 hours after admission and within 12 weeks of discharge.

They found 52 cases of CDI among 11,310 surgical admissions to four hospital units: general surgery, neurology, orthopedics and trauma. In all 52 cases, patients had a PCR-positive test result more than 72 hours after admission and within 12 weeks of discharge, making the incidence rate 0.80 cases per 1,000 patient-days. The trauma unit had the highest rate at 9.5 CDI cases per 1,000 admissions (11 cases over 1.160 admissions during the study period). General surgery had 30 cases among 3,447 admissions for a rate of 8.7; orthopedics had six cases among 4,339 admissions for a rate of 1.4; and neurology had five cases among 2,364 admissions for a rate of 2.1.

A number of risk factors were surveyed, including the use of antibiotics.

Regarding antibiotic use, the researchers found that the odds of CDI increased 3.34-fold when the perioperative antibiotic is continued more than 24 hours after surgery, outside of the perioperative window. Antibiotic use, other than the perioperative antibiotic, while in the hospital also was associated with 2.2 times greater odds of CDI. And exposure to antibiotics as long as six months before surgery increases the odds of CDI more than threefold.

“Although the surgeon cannot necessarily control the antibiotics prescribed to their patients in the year leading up to surgery, they can control antibiotic administration in the perioperative and postoperative period,” Dr. Bernatz said. “Antibiotics should be limited to one prophylactic preoperative dose, unless 24 hours of antibiotics are indicated. In the immediate postoperative period, antibiotics should be used judiciously.”

Other significant risk factors included number of hospital admissions in the past year and proton pump inhibitor or histamine type 2 receptor blocker use in the previous six months. “Previous studies have shown a correlation between CDI and hospital admission in the previous 3 months,” the researchers wrote. “Our study reports that this association extends to 12 months. We found that the number of hospital admissions in the past year increases the odds of CDI by 133% for each admission.”

A higher American Society of Anesthesiologists (ASA) physical status classification also was a significant risk factor for CDI; ASA IV or V patients were 15 times more likely to develop CDI than those with ASA class I or II disease, according to the researchers.

Dr. Bernatz said additional research is needed to further reveal these links. “Other studies could examine the rate of C. diff infection between operations within one subspecialty to determine if certain operative variables or patient characteristics affect the postoperative risk of C. diff infection,” he said.