Author Archives: cdifffoundation

Summit Therapeutics Shares New Data – Phase 2 Clinical Trial of ridinilazole for C. difficile infection (CDI)

Summit Therapeutics Reports New Data from Phase 2 Clinical Trial Connecting Ridinilazole’s Microbiome Preservation to Improved Clinical Outcomes for Patients with C. difficile Infection

October 2019

Summit Therapeutics announced the presentation of new data that explain the link between two key findings in the Company’s Phase 2 clinical trial of ridinilazole for C. difficile infection (‘CDI’):

  • Ridinilazole demonstrated superior efficacy compared to vancomycin, driven by a 60% lower recurrence rate.
  • Ridinilazole preserved the diversity of the gut microbiome.

Researchers at Tufts University, collaborating with Summit, showed that these findings are connected mechanistically by bile acids, part of the ‘metabolome’ of active chemicals made or modified by gut bacteria. Bile acids exist in different forms that can either favour or block the regrowth of C. difficile after treatment. Vancomycin kills bacteria that turn pro-C. difficile bile acids into anti-C. difficile bile acids – leaving an adverse ratio of pro- and anti-growth chemicals that favours the regrowth of C. difficile and the recurrence of C. difficile infection. By contrast, ridinilazole leaves these bacteria unharmed, allowing them to keep converting pro-C. difficile bile acids into anti-C. difficile bile acids, maintaining a positive chemical balance that prevents C. difficile recurrence.

“The damaging effect of broad-spectrum antibiotics in the treatment of CDI is far-reaching from the make-up and function of the gut microbiome through the poor clinical outcomes seen in one third of patients, driven by a high rate of disease recurrence,” said Dr David Roblin, President of R&D of Summit. “Ridinilazole has the potential to be a targeted CDI treatment that could result in significantly better patient outcomes for the over half million US patients per year who have an episode of CDI. These latest data help to put the science behind the function of a healthy microbiome into context and highlight its importance in sustaining CDI cures.”

The Phase 2 clinical trial enrolled 100 patients, half of whom received ridinilazole and the other half vancomycin. For both groups, there was a higher ratio of pro-C. difficile to anti C.-difficile bile acids at the start of treatment. This was expected, as patients who get CDI have perturbed microbiomes. However, during treatment, the proportion of anti-C. difficile bile acids increased in patients treated with ridinilazole, whereas patients treated with vancomycin initially showed decreases in anti-C. difficile bile acids and had stools dominated by pro-C. difficile bile acids. By the end of treatment, ridinilazole-treated patients’ bile acid ratios returned towards a healthy, non-CDI state. These results support the data from the Phase 2 clinical trial, in which patients receiving ridinilazole showed a statistically significant improvement in sustained clinical responses.

Copies of the two poster presentations are available in the Publications section of Summit’s website, www.summitplc.com.

To read press release and additional press releases  click on the following link to be redirected:

https://www.summitplc.com

Contagion® Interview with Ken Blount, PhD Chief Scientific Officer at Rebiotix, a Ferring Company, and Discussed the Phase II Microbiota Based RBX2660 Clinical Trial Results and Plans for Next Steps

OCT 03, 2019 | ALEXANDRA WARD

Contagion Live

To read the interview in its entirety – click on the following link to be redirected:

https://www.contagionlive.com/news/phase-2-results-microbiotabased-rbx2660-safe-efficacious-for-preventing-c-diff-recurrence

Investigators at IDWeek 2019 presented the final, 24-month analysis of data from a phase 2 open-label trial of RBX2660 for the prevention of CDI recurrence. Patients with multi-recurrent CDI were enrolled in the multicenter study and received > 2 doses of RBX2660 delivered via enema 7 days apart.

The research team defined efficacy as absence of CDI recurrence through 56 days after the last dose, and durability as continued absence of CDI episodes beyond 8 weeks. Results were compared with the 8-week recurrence-free rates for a historical control cohort that received standard-of-care antibiotic therapy.

Participant stool samples were collected prior to and for up to 720 days after treatment, and safety and durability assessments were performed at 3, 6 ,12, and 24 months. Investigators assessed microbiome changes via shallow shotgun sequencing.

https://www.contagionlive.com/news/phase-2-results-microbiotabased-rbx2660-safe-efficacious-for-preventing-c-diff-recurrence

U.S. Food and Drug Administration (FDA) Has Accepted 2 New Drug Applications (NDA) for DIFICID (fidaxomicin) In Children Aged Six Months Or Older

OCTOBER 2019

Merck

Known as MSD outside the United States and Canada

announced the U.S. Food and Drug Administration (FDA) has accepted for review a New Drug Application (NDA) for DIFICID ® (fidaxomicin) for oral suspension, and a supplemental NDA (sNDA) for a new indication for use of DIFICID tablets and oral suspension for the treatment of Clostridium (also known as Clostridioides ) difficile infections (CDI) in children aged six months or older. Both applications have received a priority review classification by the FDA. The Prescription Drug User Fee Act (PDUFA), or target action date for both applications, is set for Jan. 24, 2020. The investigational pediatric indication for DIFICID was granted Orphan Drug Designation (ODD) in 2010.

“Evidence indicates the increasing incidence of C. difficile -associated diarrhea among hospitalized children 1,” said Dr. Nicholas Kartsonis, senior vice president, Clinical Research, infectious diseases and vaccines, Merck Research Laboratories. “The filings for the pediatric indication for the new investigational oral suspension formulation of DIFICID, as well as for DIFICID tablets, underscore Merck’s focus and dedication to developing infectious disease treatments for those with unmet needs.”

The sNDA is based primarily on results of the Phase 3 SUNSHINE study 2, which were presented as part of the Late Breaker Oral Abstracts on Emerging Infections at IDWeek 2018 in San Francisco, California.

About DIFICID (fidaxomicin)

DIFICID is a macrolide antibacterial medicine indicated in adults (18 years of age or older) for treatment of Clostridium difficile -associated diarrhea (CDAD). To reduce the development of drug-resistant bacteria and maintain the effectiveness of DIFICID and other antibacterial drugs, DIFICID should be used only to treat infections that are proven or strongly suspected to be caused by Clostridiumdifficile. DIFICID is contraindicated in patients who have known hypersensitivity to fidaxomicin or any other ingredient in DIFICID. DIFICID should only be used for the treatment of C. difficile-associated diarrhea. DIFICID is not effective for the treatment of other types of infections due to minimal systemic absorption of fidaxomicin.

To review the article in its entirety click on the following link to be redirected.  Thank you.

http://www.oleantimesherald.com/business/fda-accepts-two-applications-for-merck-s-dificid-fidaxomicin-to/article_c1787f52-e9e0-5dd3-bb8c-adb22019d8b3.html

WEBINAR: Improving Care Transitions in Clostridioides difficile Infection November 14th, 2019 at 2:00 p.m. EST

WEBINAR

Improving Care Transitions in Clostridioides Difficile Infection

Thursday, November 14, 2019 at 2:00pm Eastern/11:00am Pacific

Intended Audience: Physicians, Nurse Practitioners, Physician Assistants, Nurses, Pharmacists and Case Managers

 Overview: With advances in Clostridioides difficile infection (CDI) treatment and recurrence prevention, and recently updated IDSA/SHEA guidelines, remarkable potential exists to improve CDI patient outcomes through effective interventions at critical transition points.

Join CDI experts Sahil Khanna, MD, MBBS, and Kevin Garey, PharmD, MS, FASHP, for an interactive webinar highlighting core concepts and strategies from the CDI Transitions of Care (TOC) Pathway. The CDI TOC Pathway was developed in partnership with the National Transitions of Care Coalition (NTOCC) to arm system leaders and CDI care teams with essential interventions and tools to ensure safe and effective TOCs for patients with CDI across care settings.

Agenda:

  1. Overview of the Clostridioides difficile infection (CDI) Transitions of Care Pathway
  2. How Do Ineffective Care Transitions Impact Patients with CDI?

III. Assessing CDI Risk and Implementing Diagnostic Stewardship

  1. Advances in the Treatment of Primary and Recurrent CDI
  2. Engaging CDI Patients and Caregivers in Effective and Safe Care Transitions

Expert Faculty:

Sahil Khanna, MBBS

Kevin W Garey, PharmD, MS, FASHP

Michael R Stinchon, Jr, RPH

 Offering 1.0 hour of ACCME, AAPA, AANP, ACPE, ANCC, and CCM credit.

Click on the graphic below to be directed to the webinar on

November 14th at 2:00  EST

 

 

 

 

 

 

Supporter statement: This activity is provided by PRIME Education. There is no fee to participate. This activity is supported by an educational grant from Merck & Co. Inc.

C Diff Foundation with Leading Gastroenterologist’s Oneto and Feuerstadt Announce November Clinic Dedicated for C.difficile

C Diff Foundation ( https://cdifffoundation.org/)  is a one hundred percent volunteer, world-renowned 501(c)(3) not-for-profit organization and has announced that the Foundation will offer a November clinic sponsored by the C Diff Foundation and dedicated to patients diagnosed and recovering from a C. difficile infection (CDI).

The November 19th C Diff Foundation Clinic will be hosted by Concorde Gastroenterology at their  233 Broadway Suite 840,  New York, NY 10279 office.
The clinic will hold office hours from 10:00 a.m. until  4:00 p.m. ET
With Doctor’s Caterina Oneto, MD and  Paul Feuerstadt, MD

Please call +1 212 889 5544 Ext 199
To schedule an appointment.

The August clinic received an overwhelming response from patients in various stages of recovery, including 15 individuals already scheduled with multiple spots planned for patients with recently diagnosed infection or those who have had multiple episodes and need further guidance and management.

Dr. Oneto said, “Through this clinic, we will provide access to high-level care to a number of new consults, as well as existing patients, who are recovering from the infection. It is my pleasure to partner with the C Diff Foundation and lend my expertise to the management and hopefully, eradication of this debilitating disease.”

“We are delighted with the immediate and overwhelming response from the patient community. It is a testament to the needs of those suffering from this infection. With this clinic, we hope to bring awareness, education and more importantly, cutting edge treatment to the general public,” stated Dr. Feuerstadt.

There are plans for additional clinic dates in 2020  in Florida, New York, Connecticut, Illinois, and Minnesota.

“The clinics demonstrate Doctor Oneto and Feuerstadt’s commitment over the years raising
C. diff. awareness while providing management of those suffering with
a C. diff. infection. Patients who might not otherwise be able to gain access to providers sub-specializing and caring for those with this infection will have this opportunity available.  Doctor’s Oneto and Feuerstadt’s dedication resonates within the C. diff. community and we are grateful for their participation and support.” stated Nancy Caralla, Founding President and Executive Director of the C Diff Foundation.

About C Diff Foundation

C Diff Foundation’s mission is dedicated to reaching out to communities from villages to cities, to medical practitioners, medical students, C. diff. survivors, caregivers, and the patients combating a C. difficile infection (CDI) while providing the general public important information on prevention, treatments available, clinical trials in progress, nutrition, diagnostics, and EPA registered products available for environmental safety worldwide.

About Caterina Oneto, MD

Dr. Caterina Oneto, MD is a Gastroenterologist in private practice in New York and is affiliated with NYU Langone. She completed her Fellowship in Gastroenterology at Montefiore Medical Center, Albert Einstein College of Medicine. Dr. Oneto is the Co-Director of Clinical trials at Concorde Medical Group. Her main focus is Irritable Bowel Disease (IBD),

About Paul Feuerstadt, MD

His areas of interest Clostridioides difficile infection (CDI) and ischemic diseases of the gut and in these areas he has presented his research extensively, authored and co-authored many manuscripts, textbook chapters, and online modules. Another passion of Dr. Feuerstadt is teaching, frequently giving lectures locally, regionally and nationally. He holds a clinical appointment as an Assistant Clinical Professor of Medicine at the Yale University School of Medicine and is a full-time attending physician at the Gastroenterology Center of Connecticut seeing patients with a broad spectrum of clinical gastroenterological diseases.

Dr. Feuerstadt attended the Weill Medical College of Cornell University in Manhattan for medical school and completed his residency in internal medicine at New York-Presbyterian Hospital/Weill Cornell. His clinical fellowship training was completed at Montefiore Medical Center in the Bronx, New York.

Clostridioides difficile infections (AKA C. diff., C.difficile, CDI) and Microbiome modification.
Dr Oneto is also Co-Director of the C.diff. Community Global Support program offered by the
C Diff Foundation.  Dr. Oneto appears regularly on Doctor Radio on Sirius Xm
and C. diff. Spores and More Radio (cdiffradio.com).

About C.difficile

It is the most common Healthcare-associated infection affecting an estimated 450,000 people annually in the United States alone with ~28,000 deaths from complications of this infection. This infection accounts for ~16% of all healthcare-associated infections.

In the USA: Nearly half a million Americans suffer from Clostridioides difficile (C. diff.) infections in a single year according to a study released on February 25, 2015, by the Centers for Disease Control and Prevention (CDC).

**Approximately 29,000 patients died within 30 days of the initial diagnosis of C. difficile. Of those, about 15,000 deaths were estimated to be directly attributable to C. difficile infections (CDI), making C. difficile a very important cause of infectious disease death in the United States alone. More than 80 percent of the deaths associated with C. difficile occurred among Americans aged 65 years or older. C. difficile causes an inflammation of the colon and deadly diarrhea.

C. difficile clade A, Able to Withstand Modern Diet and Healthcare Facilities Long Before They Existed

Researchers at The Wellcome Sanger Institute and the London School of Hygiene & Tropical Medicine say they found that C. diff bacteria appears to have broken off into another species, reports StudyFinds.

While the researchers just uncovered the strain, it’s likely been around for tens of thousands of years and is probably the cause of the majority of C.diff infections at hospitals today.

The strain, which is being called C. difficile clade A, was built to withstand modern diet and healthcare facilities way before they existed.

Scientists say that Clostridium difficile (C. diff) is evolving, which could make things more difficult for hospitals that have for years struggled with the bacteria.

The newly discovered strain are problematic because they prefer the sugar-rich diet enjoyed in western countries and can tolerate the cleaning procedures typically carried out at the healthcare facilities in these countries. (*?)

Those involved in the study say it has provided scientists with a better understanding of how bacteria evolves over time. They say the discovery further proves the importance of genomic studies of bacteria.

Another study conducted by the American Society for Microbiology recently found that C. diff is doing a good job of sticking to hospital gowns even after they’ve been treated.

Cephamycin and Vancomycin Prevent C. difficile infection (CDI) recurrence Discovered by Researchers

Abstract

Spore-forming bacteria encompass a diverse range of genera and species, including important human and animal pathogens, and food contaminants. Clostridioides difficile is one such bacterium and is a global health threat because it is the leading cause of antibiotic-associated diarrhoea in hospitals.

A crucial mediator of C. difficile disease initiation, dissemination and re-infection is the formation of spores that are resistant to current therapeutics, which do not target sporulation. Here, we show that cephamycin antibiotics inhibit C. difficile sporulation by targeting spore-specific penicillin-binding proteins.

Using a mouse disease model, we show that combined treatment with the current standard-of-care antibiotic, vancomycin, and a cephamycin prevents disease recurrence.

Cephamycins were found to have broad applicability as an anti-sporulation strategy, as they inhibited sporulation in other spore-forming pathogens, including the food contaminant Bacillus cereus. This study could directly and immediately affect treatment of C. difficile infection and advance drug development to control other important spore-forming bacteria that are problematic in the food industry (B. cereus), are potential bioterrorism agents (Bacillus anthracis) and cause other animal and human infections.

To review abstract in its entirety please click on the following link to be redirected:

https://www.nature.com/articles/s41564-019-0519-1