Category Archives: Recurrent C. diff. Prevention Clinical Trials

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:

PDF Document

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.

Seres Therapeutics Announced on March 30th, 2020, That the Company Has Completed Enrollment of its SER-109 Phase 3 Clinical Study, ECOSPOR III

On March 30th, 2020

Seres Therapeutics, Inc., announced that the Company has completed enrollment of its SER-109 Phase 3 clinical study, ECOSPOR III.

www.serestherapeutics.com

 

SER-109 is an oral, first-in-field microbiome therapeutic candidate that has been granted Orphan Drug and Breakthrough Therapy designations by the U.S. Food and Drug Administration (FDA), and is being investigated for use in preventing recurrent Clostridium difficile infection (CDI).

“We are pleased to have achieved this critically important corporate milestone. SER-109 has the potential to be the first FDA-approved therapy for C. difficile infection to treat the underlying cause of this disease, and the first approved microbiome drug for any human condition. We believe SER-109 could fundamentally transform the treatment of patients with recurrent C. difficile infection, a life-altering infectious disease, and we eagerly look forward to topline clinical results in the middle of this year. With compelling Phase 3 ECOSPOR III clinical data, we plan to engage in discussions with the FDA regarding a filing for product approval,” said Eric Shaff, President and Chief Executive Officer of Seres. “We are also working to advance our other promising clinical development candidates in light of the COVID-19 pandemic. This remains an evolving situation and we are carefully reviewing our development plans to determine how to rapidly advance our pipeline toward high-quality data readouts.”

SER-109 Study Updates

The SER-109 Phase 3 ECOSPOR III study (ClinicalTrials.gov identifier: NCT03183128) is a multicenter, randomized, placebo-controlled study which has enrolled 181 patients with multiply recurrent CDI to date. ECOSPOR III had been designed to enroll 188 patients. The Company has decided to halt enrollment as a result of the COVID-19 pandemic. Seres believes that ECOSPOR III remains well-powered to evaluate the efficacy of SER-109. The ECOSPOR III study’s primary endpoint is the reduction of CDI recurrence at up to eight weeks following SER-109 administration, and the Company expects to report study results in mid-2020 as had been planned.

Seres is grateful to the patients, principal investigators and clinical research teams who participated in ECOSPOR III, many of whom are now involved in the fight against COVID-19.

The SER-109 Phase 3 ECOSPOR III study includes use of an objective Clostridium difficile cytotoxin assay to ensure that all patients entering the study have active CDI, as well as to confirm CDI recurrences during the study (i.e., the ECOSPOR III primary endpoint).

Seres plans to initiate a SER-109 Expanded Access Program at selected clinical sites participating in the ongoing Phase 3 ECOSPOR III study, and the Company may also initiate the program at additional clinical sites for eligible patients to have access to SER-109.

Prior completed clinical studies have demonstrated SER-109 bacterial engraftment into the gastrointestinal microbiome, and that engraftment is associated with reduced recurrence of CDI. In all prior clinical studies, SER-109 was associated with a favorable safety profile.

The FDA has issued several safety alerts related to Fecal Microbiota Transplantation (FMT) and the risk of pathogen transmission including warnings related to Multi-Drug Resistant Organisms and SARS-CoV-2, the virus linked to COVID-19 (June 12, 2019Alert; March 12, 2020Alert; and March 23, 2020Alert). Unapproved FMT is widely used under an FDA Enforcement Discretion policy for the treatment of recurrent CDI that is not responsive to standard therapies.

In contrast to FMT, SER-109 is comprised of a highly purified consortia of spore-based commensal bacteria and is manufactured under Good Manufacturing Practices (GMP) conditions using stringent standards to ensure product quality and consistency. Seres utilizes a unique manufacturing process which has been demonstrated to inactivate numerous potential pathogens, including species of non-spore bacteria, such as Escherichia coli, and viruses. The Company’s manufacturing process inactivates many emerging potential pathogens where diagnostic assays may not yet be available, such as SARS-CoV-2. Seres has issued a position statement highlighting the criticality of including pathogen inactivation processes in the manufacture of microbiome therapeutics. Recent discussions with the FDA have indicated agency support regarding the fundamental differentiation between FMT and Seres’ product candidates.

COVID-19 Impact and Other Clinical Program Updates

Seres continues to monitor the impact of the COVID-19 pandemic on Company operations and ongoing clinical development activity, including the SER-287 Phase 2b study in ulcerative colitis, the SER-401 Phase 1b study in metastatic melanoma, and SER-301, a rationally designed, fermented development candidate for ulcerative colitis. Mitigation activities to minimize COVID-19-related operation disruptions are ongoing; however, given the severity and evolving nature of the situation, the timing of SER-287 Phase 2b and SER-401 Phase 1b clinical readouts is uncertain. Seres does not anticipate disruptions to the availability of its drug product candidates for ongoing studies.

The SER-287 Phase 2b study is currently approximately 60% enrolled based on the 201-patient target study size. SER-287 development activity has been adversely impacted by multiple clinical sites halting non-essential procedures, including endoscopies, which may make it difficult to achieve the original enrollment target in H2 2020 as planned. Seres is evaluating enrollment mitigation strategies and possible trial design modifications with the goal of obtaining a high-quality, clinically meaningful dataset within a timeframe consistent with Seres’ prior guidance for its cash runway extending into the second quarter of 2021. Furthermore, the Company is encouraged by the FDA’s indications of flexibility in light of the COVID-19 pandemic, and plans to engage the FDA in discussions regarding any potential trial modifications.

Seres continues to execute on activities to advance SER-301 clinical development and the planned initiation of patient dosing in Australia and New Zealand later this year.

 

SOURCE:  http://ir.serestherapeutics.com/news-releases/news-release-details/seres-therapeutics-announces-completion-enrollment-ser-109-phase

U.S. Food and Drug Administration (FDA) Grants Breakthrough Therapy Designation to Finch Therapeutics Investigational Drug CP101 for Treatment of Recurrent Clostridium difficile Infection (rCDI)

Finch Therapeutics Group, Inc., a clinical-stage microbiome therapeutics company, announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to investigational drug CP101 for the treatment of patients with recurrent Clostridium difficile (C. difficile) infection. Breakthrough Therapy Designation is intended to expedite the development and review of investigational therapeutics for serious or life-threatening conditions where preliminary clinical evidence indicates that the product may demonstrate a substantial improvement over existing therapies on one or more clinically significant endpoints.

Finch’s lead therapeutic candidate CP101 is designed to prevent recurrent C. difficile, a bacterial infection affecting over 500,000 patients each year and leading to an estimated 29,000 annual deaths. Recurrent C. difficile has been named an urgent public health threat by the Centers for Disease Control (CDC) and, with a high percentage of patients failing standard-of-care antibiotic treatment, presents a clear and urgent unmet medical need.

“We are thrilled that CP101 has been designated as a Breakthrough Therapy for recurrent C. difficile,” said Mark Smith, CEO of Finch. “CP101 is designed to break the cycles of infection by restoring the balance of the gut microbiome, an approach supported by numerous clinical studies and Finch’s extensive experience providing microbial treatments to patients suffering from C. difficile. This designation will accelerate our efforts to provide an effective therapy for patients living with this devastating infection, and we look forward to working closely with the FDA to advance that mission.”

Finch is actively enrolling patients with recurrent C. difficile in PRISM3, a randomized, placebo-controlled Phase II clinical study to assess the safety and efficacy of CP101. The study drug is an oral capsule that is administered in a single dose. For more information about this trial, please visit www.prism3trial.com.

CP101 is not approved in any country.The FDA’s Breakthrough Therapy Designation does not constitute or guarantee a future approval and does not alter the standards for approval.

About Finch Therapeutics Group, Inc.Finch Therapeutics Group, Inc. (Finch) is developing novel microbial therapies to serve patients with serious unmet medical needs. Built on 30 years of translational research at OpenBiome, MIT, University of Minnesota and the Center for Digestive Diseases, Finch uses  Human-First Discovery  to develop therapies from microbes that have demonstrated clinically significant impacts on patient outcomes. Finch is unique in having both a donor-derived  Full-Spectrum Microbiota  ( FSM ) product platform and a  Rationally Selected Microbiota  ( RSM ) product platform based on microbes grown in pure culture. Finch’s lead program, CP101, is an investigational  FSM  product for prevention of recurrent  C. difficile  infections. Finch’s  RSM  platform employs machine-learning algorithms to mine Finch’s unique clinical datasets, reverse engineering successful clinical experience to identify the key microbes driving patient outcomes. Finch has a strategic partnership with Takeda to develop FIN-524, an investigational  RSM  product for inflammatory bowel disease. Finch is using a rich foundation of clinical data to advance its pipeline, leveraging proof-of-principle results to evaluate target indications and inform the design of this new therapeutic class.

Full-Spectrum Microbiota, FSM, Rationally-Selected Microbiota, RSM, and Human-First Discovery are trademarks of Finch Therapeutics Group, Inc.

View source version on businesswire.com:https://www.businesswire.com/news/home/20190208005039/en/

Learn More About Clostridium difficile (C.diff., C.difficile) infection and Recurrent CDI Clinical Trials In Progress

 

 

 

The C Diff Foundation has implemented a global campaign to raise awareness of Clostridium difficile infection (C.difficile) clinical trials, clinical studies, clinical research and observational studies evaluating interventions for C. difficile prevention, treatments, and environmental safety.

In the USA: Nearly half a million Americans suffer from Clostridium difficile (C. diff.) infections in a single year according to a study released in 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 making C. difficile a very important cause of infectious disease death in the United States.

“Clostridium difficile infections are not only the most common cause of healthcare-acquired infections in the United States but also very common in the community in younger patients who previously were thought to be less susceptible to C. difficile. The rate of recurrent C. difficile infections is increasing tremendously and this increase is higher than the rate of primary C. difficile infections,” stated Sahil Khanna, MD, Assistant Professor of Medicine Division of Gastroenterology and Hepatology, Director of the C. difficile Clinic, Fecal Microbiota Transplantation program and C. difficile related Clinical Trials, Mayo Clinic, Rochester, MN.

Dr. Khanna also added, “It is imperative and important for clinical trials to be done to advance the development of new treatments, new medications, and new ways to prevent and treat Clostridium difficile infections.”

Individuals volunteer to participate in clinical trials in hopes of improving their own health, to access treatments that might not be available otherwise, often because they are new and not yet widely available. They help others by contributing to advances in medicine. There can also be potential risks participating in clinical trials and clinical studies. All of the known risks associated with a particular trial and or study will be discussed during the informed consent process. It will be thoroughly explained in the informed consent document that a volunteer will receive from the research staff prior to participating in any study.

To learn more about clinical research (e.g., Clostridium difficile, C.difficile) visit the U.S. Food and Drug Administration http://www.fda.gov or telephone 1-800-835-4709, The National Institutes of Health (NIH) http://www.nih.gov and ClinicalTrials.gov.

“Clinical trials are vital to improving our knowledge about how best to prevent and treat C. difficile infections. Informing patients of clinical trials is important, and in recent years several clinical trials have led to significant improvements in the treatments available for patients with C. difficile infections,” stated Mark Wilcox, MD, FRCPath, Consultant Microbiologist, Head of Microbiology and Academic Lead of Pathology Leeds Teaching Hospitals, Professor of Medical Microbiology University of Leeds Institute of Biomedical and Clinical Sciences, Lead on Clostridium difficile for Public Health England, UK.

About the U.S. Food and Drug Administration (FDA):
The FDA is responsible for protecting the public health by assuring that foods are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drug, and vaccines and other biological products and medical devices intended for human use are safe and effective. FDA’s responsibilities extend to the 50 United States, the District of Columbia, Puerto Rico, Guam, the Virgin Islands, American Samoa, and other U.S. territories and possessions.

About the National Institutes of Health (NIH):
The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency making important discoveries that improve health and save lives.

About ClinicalTrials.gov
ClinicalTrials.gov is a Web-based resource that provides patients, their family members, health care professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions.

Zinplava has been launched by MSD in the UK

MSD has launched Zinplava in the UK, offering patients a novel therapeutic option for the prevention of Clostridium difficile recurrence.

Zinplava (bezlotoxumab) is not an antibacterial and is not indicated to actually treat the infection, but is a monoclonal antibody designed to neutralise C. difficile toxin B, which can damage the gut wall and cause inflammation, leading to diarrhoea.

It is the first and only EC licensed non-antibiotic option indicated to prevent recurrence of Clostridium difficile infection (CDI) in high-risk adults.

Around one-in-four patients experience a recurrence after the initial episode, and more than 40 percent of these have further recurrence, highlighting the need for new options able to break the infection cycle.

Pivotal Phase III clinical studies showed the rate of infection recurrence through week 12 to be significantly lower in patients given Zinplava (17.4 percent and 15.7 percent) or Zinplava and actoxumab (15.9 percent and 14.9 percent) than those taking a placebo (27.6 percent) and (25.7 percent), respectively.

“Notably, bezlotoxumab reduces the risk of the recurrence of CDI for at least 3 months, compared with standard of care antibiotic therapy. This is welcome addition to our limited options to reduce the considerable morbidity and mortality associated with CDI,” commented Mark Wilcox, Professor of Medical Microbiology at the University of Leeds.

“Antimicrobial resistance is a key national issue and we hope with bezlotoxumab to not only help achieve a reduction in the number of recurrent episodes of CDI but also a reduction in the amount of antibiotic prescriptions that would otherwise be needed to treat these recurrent episodes,” added Dr Mike England, MSD’s Interim Medical Director.

Zinplava is administered as a single, one-off, one-hour intravenous infusion alongside standard-of-care antibiotic therapy for the treatment of CDI.