Tag Archives: Are there clinical trials for recurrent C. difficile infections?

Microbiota Restoration Therapy (MRT) (Drug Platform) Reduces Antibiotic-resistant Bacteria Gut Colonization In Patients with Recurrent C. difficile Infection (rCDI)

Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study

Abstract

Background

Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI.

Methods

An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms.

Results

Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted.

Conclusions

Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others.

Trial registration

ClinicalTrials.gov, NCT01925417; registered on August 19, 2013.

 

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

https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00843-9#citeas

Seres Therapeutics and Nestle’ Health Science Team Up For the Joint Commercialization of Seres Therapeutics Investigational Microbiome Treatment for Recurrent C. difficile Infection (rCDI)

Seres Therapeutics and Nestlé Health Science have announced a decision to team up for the joint commercialization of Seres’s investigational oral microbiome treatment for recurrent Clostridioides difficile (C. difficile) infections (CDI).

Nestlé Health Science had previously received commercial rights to Seres’s therapeutics for inflammatory bowel disease and CDI, but only outside the U.S. and Canada. This expansion places Nestlé as Seres’s global collaborator for SER-109, a therapy the company hopes to treat a leading contributor to hospital-acquired infections in North America. If approved by the U.S. Food and Drug Administration (FDA), the agent, dubbed SER-109, will be the first microbiome therapeutic available.

Each year, CDI contributes to the deaths of 20,000 Americans. Standard of care for recurrent CDI includes the use of fecal microbial transplants. Currently, there is no microbiome therapies approved for any indications, which has created an unmet need recognized by an ever-growing list of pharmaceutical companies partnering with microbiome startups.

Seres’s investigational SER-109 includes purified Firmicutes spores; the rationale for including these spores is “based on their modulatory role in the life cycle of C. difficile and disease pathogenesis,” according to a statement made by the company.

Findings from the pivotal Phase III ECOSPOR III trial announced back in August 2020 showed SER-109 significantly reduced the CDI recurrence rate compared with placebo over an eight-week period. The absolute reduction of the CDI recurrence rate was 27% while the relative risk reduction was 68%. In addition, up to 88% of patients experienced a sustained clinical response by the end of the eight weeks.

Nestlé Health Science has agreed to use Aimmune Therapeutics, the company’s global pharmaceutical business, to lead the commercialization of the therapy. In return, Seres has agreed to receive upfront licensing payments totaling $175 million. An additional $125 million will be paid to Seres by Nestlé upon FDA approval of the microbiome agent.

Under terms of the agreement, Seres holds the sole responsibility for costs associated with development and pre-commercialization of SER-109 in the U.S. The company will be eligible to receive up to 50% of the commercial profits once the therapeutic is commercialized.

“Nestlé Health Science has been a terrific collaborator in our quest to develop a new treatment option for patients suffering from recurrent C. difficile infection, and their support over the past few years has been critical in advancing SER-109 to address this unmet need,” said Eric Shaff, Seres Therapeutics’ chief executive officer, in a statement. “As we prepare for potential approval and commercialization, we are eager to embark side-by-side on our next phase with a company that believes as fervently as we do in the potential of this transformative approach to reduce the recurrence of CDI.”

Nestlé Health Science’s CEO, Greg Behar, added that the company “is focused on the fast-developing areas of gut health, food allergies and metabolic health within our global pharmaceutical business, Aimmune Therapeutics.” As such, Aimmune’s “fully integrated commercial infrastructure” will be leveraged to launch the therapy, pending approval.

Seres has been busy this year in moving its investigational microbiome therapy pipeline in front of the FDA. Last month, Seres announced the agency had cleared an Investigational New Drug application for the company’s other investigational microbiome therapeutic for preventing antibiotic-resistant bacterial infections as well as graft-versus-host disease.

The company is advancing SER-155 into a Phase Ib trial under a collaboration with Memorial Sloan Kettering Cancer Center. “SER-155 represents a novel microbiome technology with the potential to address antibiotic-resistant bacterial bloodstream infections and further to modulate host immunomodulatory responses to decrease graft-versus-host disease,” said Seres’s chief scientific officer, Matthew Henn, Ph.D., in a statement.

 

SOURCE:  https://www.biospace.com/article/seres-nestle-agree-to-jointly-commercialize-microbiome-agent-for-c-diff-infections/

Patient, Family, Caregiver January Symposium Broadcasts During March On C. diff. Spores and More Live Program

CDIFFRADIO.COM

 

 

 

 

 

 

 

SAVE THE DATES to listen in to the leading topic expert presentations

shared on January 15, 2021, at the Patient, Family, Caregiver Symposium:

Beginning Tuesday, March 9 from 1:00 p.m. – 2:00 p.m. EST following through on

March 16,  March 23, and  March 30.

A Symposium specifically developed for Patients Diagnosed With a C. diff. Infection, Being Treated For a Clostridioides diffiicile infection, Recovering From a Clostridioides difficile Infection and Recurrences with Family Members and Caregivers.

The Patient & Family C. diff. Symposium was a gathering of healthcare professionals, keynote speakers, health advocates, practitioners, educators, thought leaders, and patients who are transforming the patient experience and changing the way people experience
C. diff. infections worldwide.

Unlike other conferences on this topic, patients will share their C. diff. infection journeys, providing a real-world perspective on patient experience. Our attendees will learn more from this virtual-online symposium and gain knowledge on important topics that will better aid their care and recovery through tools and strategies delivered by keynote speakers.  

The Symposium followed the C Diff Foundation Mission statement –   Educating and Advocating for the prevention, treatments, clinical trials, diagnostics, and environmental safety of Clostridioides difficile
(C. diff.) infections worldwide.

Keynote speakers presented up-to-date data to expand on the existing knowledge and provide important information focused on, yet not limited to,  a Clostridioides difficile infection (also known as C. diff., C. difficile, CDAD, CDI) ……

  • Prevention
  • Treatments
  • Diagnostics
  • Research
  • Environmental Safety
  • Clinical trials and studies

WITH

  • Introduction to Microbiome Research and Studies
  • Infection Prevention
  • Fecal Microbiota Restoration and Transplants
  • Antibiotic Stewardship

We hope you enjoy the broadcasts!

 

Program Chair:  Paul Feuerstadt, MD, FACG

Barbara McGovern, MD     “Treatment of recurrent C. difficile infection with                                                                                        SER-109, an investigational microbiome drug.”

Paul Feuerstadt, MD          ” C. diff. Overview – What is a C. diff. Infection?”

Sahil Khanna, MD               “C. diff. Treatments + FMT Overview. “

 

 

 

Simon Cutting, Ph. D.         “Bacillus, and C. diff.  Spore Overview. “

Teena Chopra, MD                ” Introduction to Infection Prevention.”

Doe Kley, RN, MPH              “C. diff. Transitioning from Hospital to Home. “

Courtney Jones                    ” Microbiome, Microbiota, and Gut Health.”

Denise Cardo, MD                “Everyone Has a Role in Antibiotic Awareness.”

Larry Kociolek, MD              “C. diff. Infections in Pediatrics.”

Kathy Bischoff                        “My C. diff.  Journey.”

Renata Johnson                      “My C. diff. Journey.”

Paul Feuerstadt, MD      &    Barbara McGovern, MD

 

This Symposium was hosted by the C Diff Foundation and

Sponsored by Seres Therapeutics  

Destiny Pharma Update On the Acquired NTCD-M3 Biotherapeutic Clinical Program For Prevention of Recurrence of C. diff. Infections (rCDI)

Update on the recently acquired NTCD-M3 biotherapeutic clinical programme for prevention of recurrence of C. difficile infections

Press release by Destiny Pharma:

Brighton, United Kingdom – 22 December 2020: Destiny Pharma plc (AIM: DEST) a clinical-stage innovative biotechnology company focused on the development of novel medicines that can prevent life-threatening infections, announces it is making good progress with preparations for the clinical development of NTCD-M3, a Phase 3 ready biotherapeutic for the prevention of C. difficile infection (CDI) recurrence.

Following the successful fundraising of £10.4 million in November 2020 and completion of the acquisition of NTCD-M3, Destiny Pharma has commenced the work required to prepare for the Phase 3 clinical study that is scheduled to start in 2022.

Also, Professor Dale Gerding has joined Destiny Pharma’s Scientific Advisory Board (SAB) and is working as a key consultant. His world-leading expertise in C. difficile infections and many years of research and clinical work on NTCD-M3 will be invaluable and he is an important addition to our team.

Destiny Pharma has also signed a major new contract with a leading biotherapeutics manufacturing company for the establishment of a new NTCD-M3 process for the production of the Phase 3 clinical trial doses. Establishing the new manufacturer will deliver a more efficient process and a lower-cost product and is an important investment in the overall NTCD-M3 project. The Company is also starting business development efforts and will reach out to potential commercial partners and grant funding bodies to raise awareness of the re-activated NTCD-M3 clinical programme.

In the US, there are approximately 500,000 cases of CDI each year; around 25% of these initial cases then recur leading to 29,000 deaths per year. Current CDI treatment options are limited with lower efficacy observed when patients are retreated with the same antibiotic for recurrence of CDI. The extra costs of care in the US per CDI patient range from $10,000 to $20,000 and the total annual CDI-attributable cost in the US alone is estimated in 2016 at $6.3 billion.

Dr. Bill Love, Chief Scientific Officer of Destiny Pharma, said, “We are very pleased to have started activities immediately on our new NTCD-M3 project. Setting up the new manufacturing process is a key step to deliver the doses of NTCD-M3 product required for the single, 800 patient Phase 3 study required by the US FDA. The work will also look at scaling up the process towards commercial supply. We look forward to announcing further progress in 2021.”

Professor Dale Gerding, the discoverer of NTCD-M3, and member of Destiny Pharma’s SAB, added: “I am enthusiastic about the resumption of the final phase of development of NTCD-M3 and welcome the opportunity to work with Destiny Pharma to bring it to patients. As a C. difficile clinician and researcher for nearly 40 years, my mission has been to see this terrible infection prevented. Everything that has been done to date suggests that NTCD-M3 will provide the preventive strategy needed to not only prevent recurrence of C. difficile infection but to also prevent it from ever occurring in the most vulnerable patients.”

Inquiries:

Destiny Pharma plc
Neil Clark (Chief Executive Officer)
Shaun Claydon (Chief Financial Officer and Company Secretary)
+44 (0) 1273 704 440

finnCap Limited – Nominated Adviser and Joint Broker
Geoff Nash / Kate Bannatyne / Charlie Beeson (Corporate Finance)
Alice Lane (ECM)
+44 (0) 20 7220 0500

WG Partners LLP – Joint Broker
Nigel Barnes / Claes Spång / Nigel Birks / Andrew Craig
+44 (0) 20 3705 9330

Optimum Strategic Communications
Mary Clark / Shabnam Bashir / Manel Mateus
+44 (0) 203 174 1789

About NTCD-M3
NTCD-M3 (non-toxigenic C. difficile strain M3) was developed by the US infectious diseases physician, Professor Dale Gerding, who is a world-leading specialist in C. difficile infection, with more than 400 peer-reviewed journal publications, book chapters, and review articles in the area. NTCD-M3 has successfully completed Phase 1 and Phase 2b trials. The Phase 1 study demonstrated a strong safety/toxicology profile and Phase 2b showed that the best dose delivered a 95% prevention of CDI recurrence. The Phase 2b NTCD-M3 data was published in the prestigious Journal of the American Medical Association (Gerding DN et al JAMA
2015;313:1719).

C. difficile NTCD-M3 is a naturally occurring non-toxigenic strain of C. difficile bacteria, which lacks the genes that can express C. difficile toxins. It is an oral formulation of NTCD-M3 spores and patients who have taken NTCD-M3 were found to be protected from recurrence of C. difficile infections. NTCD-M3 acts as a safe “ground cover” preventing toxic strains of C. difficile proliferating in the colon after antibiotic treatment. NTCD-M3 temporarily colonizes the human gut without causing any symptoms allowing the gut microbiome time to recover following antibiotic treatment.

About Destiny Pharma
Destiny Pharma is a clinical-stage, innovative biotechnology company focused on the development of novel medicines that can prevent life-threatening infections. Its pipeline has novel microbiome-based biotherapeutics and XF drug clinical assets including NTCD-M3, a Phase 3 ready treatment for the prevention of C. difficile infection (CDI) recurrence which is the leading cause of hospital-acquired infection in the US, and also XF-73 nasal gel, which is in a Phase 2b clinical trial targeting the prevention of postsurgical Staphylococcal hospital infections including MRSA. It is also co-developing SPOR-COV, a novel, biotherapeutic product for the prevention of COVID-19 and other viral respiratory infections, and has earlier grant-funded XF research projects.

For further information, please visit https://www.destinypharma.com