Tag Archives: Seres Therapeutics SER-109

Seres Therapeutics Announces a New SER-109 Phase 2 Clinical Study (ECOSPOR III) For Patients With Multiple Recurrent C. diff. Infections (CDI’s)

Seres Therapeutics Inc. a leading microbiome therapeutics platform company, announced on March 16th, 2017 plans to initiate a new SER-109 Phase 2 clinical study (ECOSPOR III) in patients with multiply recurrent Clostridium difficile (C. difficile) infection. The ECOSPOR III study design was finalized following a positive Type B meeting with the U.S. Food and Drug Administration (FDA). In a separate announcement today, Seres reported fourth quarter and full year 2016 financial results and provided an update on multiple ongoing microbiome clinical programs.

Seres plans to initiate a new SER-109 clinical study in approximately 320 patients with multiply recurrent C. difficile infection. Study participants will be randomized 1:1 between SER-109 and placebo. To ensure accurate measurement of C. difficile infection, diagnosis of recurrent C. difficile infection for both study entry and for endpoint analysis will be confirmed by C. difficile cytotoxin assay. Patients in the SER-109 arm will receive a total SER-109 dose, administered over three days, approximately 10-fold higher than the dose used in the prior ECOSPOR study. ECOSPOR III will evaluate patients for 24 weeks and the primary endpoint will compare the C. difficile recurrence rate in subjects who receive SER-109 verses placebo at up to eight weeks after dosing. The FDA has agreed that this new trial may qualify as a pivotal study with achievement of a persuasive clinical effect and addressing FDA requirements, including clinical and statistical factors, an adequately sized safety database, and certain CMC parameters.

“We are pleased to have received highly constructive guidance from the FDA regarding further SER-109 clinical development and we plan to initiate a new clinical study as soon as possible,” said Roger J. Pomerantz, M.D., President, CEO and Chairman of Seres. “Our prior SER-109 studies provided important new biological and clinical data that have advanced our pioneering microbiome therapeutic efforts. Based on our learnings and dialogue with the FDA, we believe that we are now positioned to initiate a robust clinical study that may provide the basis for SER-109 approval. There is an urgent need for improved treatments for C. difficile infection, and we believe SER-109 has great potential to address the underlying cause of the disease and become the first approved microbiome therapeutic in this new field of medicine.”

About SER-109

SER-109, an oral capsule, is Seres’ lead Ecobiotic® microbiome therapeutic for the treatment of multiply recurrent C. difficile infection. SER-109 is a biologically sourced consortium of bacterial spores designed to catalyze a shift in a dysbiotic gastrointestinal microbiome to a healthier state.

About Seres Therapeutics

Seres Therapeutics, Inc. is a leading microbiome therapeutics platform company developing a novel class of biological drugs that are designed to treat disease by restoring the function of a dysbiotic microbiome, where the natural state of bacterial diversity and function is imbalanced. The Phase 2 study of Seres’ program SER-109 has been completed in multiply recurrent Clostridium difficile infection. Seres’ second clinical candidate, SER-287, is being evaluated in a Phase 1b study in patients with mild-to-moderate ulcerative colitis (UC). Seres is also developing SER-262, the first ever synthetic microbiome therapeutic candidate, in a Phase 1b study in patients with primary CDI. For more information, please visit www.serestherapeutics.com. Follow us on Twitter @SeresTx.

Forward-looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding SER-109 development plans, the timing, design, and results of the ECOSPOR III study , the potential for ECOSPOR III to provide different results than the previous ECOSPOR study, the impact analysis of prior clinical studies may have on clinical outcomes, the potential for ECOSPOR III to qualify as a Pivotal Study, dysbiosis as an underlying cause of C. difficile and other diseases.

To Read article in its entirety please click on the link below:

http://finance.yahoo.com/news/seres-therapeutics-initiate-ser-109-110000650.html;_ylt=AwrBT.EHTNBYMRUAv3hXNyoA;_ylu=X3oDMTEzbjcwdjAxBGNvbG8DYmYxBHBvcwM4BHZ0aWQDVUkwMkM0XzEEc2VjA3Ny

 

 

Seres Therapeutics Share Key Findings From Earlier Reported SER-109 Phase 2 Clinical Study Outcome

seres-therapeutics-inc-logo

As published in Seres Therapeutics Press Release  January 31, 2017

 

Findings suggest that both misdiagnosis of C. difficile recurrent infection in some patients, and dosing that may have been suboptimal in certain patients, contributed to the previously reported SER-109 Phase 2 study outcome –

FDA discussions are ongoing regarding a new, redesigned clinical study for SER-109

CAMBRIDGE, Mass., On January 31, 2017 —Seres Therapeutics Inc., a leading microbiome
therapeutics platform company, reported that it has completed in-depth analyses of the previously reported SER-109 Phase 2, eight-week clinical study data in patients with multiply recurrent Clostridium difficile infection.

The company also reported the full, 24-week SER-109 Phase 2 study results and open label extension study data.

“Since obtaining the unexpected SER-109 clinical study results last summer, we have undertaken a comprehensive assessment of the program to understand the reasons for the results,” said Roger J. Pomerantz, M.D., President, CEO and Chairman of Seres.

“We have now identified specific factors that we believe contributed to the Phase 2 results, including issues related to both the accurate diagnosis of C. difficile recurrent infection, and potential suboptimal dosing of certain subjects in the trial. The SER-109 analyses were recently shared with the FDA, and we are actively discussing the design of a new clinical trial for SER-109. There remains a compelling need for an effective, safe, and convenient FDA approved therapy for patients with recurrent C. difficile infection, and this investigation provides insights to guide further clinical development of SER-109.”

Investigation Summary: C. difficile Diagnosis: Analysis was conducted to evaluate both the role of C. difficile diagnostic testing in defining the correct SER-109 Phase 2 study entry population, and in the proper diagnosis of C. difficile recurrences during the study. In the Phase 2 study, 81% of study subjects (72 of 89 subjects) were enrolled based on polymerase chain reaction (PCR) based testing for C. difficile, as well as clinical evaluation. An important and increasingly well-appreciated limitation of PCR testing is that while a positive result indicates that C. difficile cytotoxin genes are present, a positive PCR test does not necessarily indicate thatthe organism is viable and producing disease causing cytotoxins, nor that
C. difficile is the source of clinical symptoms.1

Two separate observations were made pertaining to the effects of discordant results from PCR and cytotoxin assay on the SER-109 trial. The qualifying stool samples evaluated for Phase 2 study entry were not available for retesting for cytotoxin, however, the company was able to retest the samples associated with patients entering the open label extension trial for the presence of the C. difficile cytotoxin and determined that only 44% of samples (15 of 31 subjects) that tested positive by PCR testing also tested positive based on C. difficile cytotoxin assay. These results suggest that a substantial proportion of patients who entered the SER-109 Phase 2 study may have been C. difficile carriers and, therefore, C. difficile infection may not have been the source of the clinical symptoms. In addition, data from this analysis suggest that the use of PCR to measure C. difficile may have overestimated study recurrences in both treatment arms of the Phase 2 trial, further complicating interpretation of study results. This was shown by reanalysis of samples with cytotoxin assay, from patients diagnosed as recurrent in the Phase 2 study. In this retesting, between one quarter andone half of presumed study recurrences may not have been true C. difficile infections leading to pathology.

From the analyses described above, the company believes that misdiagnoses may have occurred both in some patients entering the SER-109 trial, as well as for recurrences diagnosed during the trial.

SER-109 Pharmacokinetics, Pharmacodynamics, & Dosing

The company performed an in-depth analysis to examine SER-109 biological activity in the Phase 2 trial, as measured by microbiome changes in patients and downstream biological effects in the gastrointestinal tract. Results demonstrated a statistically significant increase in the richness of commensal spore-forming bacterial species in patients treated with SER-109, as compared to those receiving placebo. These data demonstrate that SER-109 successfully engrafted and was biologically active in the Phase 2 study. In addition, among those patients with an increased prevalence of specific SER-109 associated bacterial species, a decreasedrate of high confidence recurrences (i.e., recurrences confirmed by C. difficile cytotoxin assay) was demonstrated.

The company also assessed whether the SER-109 dose impacted the degree of microbiome changes observed. All Phase 2 patients received 1 X 10 8 bacterial spores, whereas patients in the prior SER-109 Phase 1b open label study received doses ranging approximately 700-fold, from 3 X 107 to 2 X 109 spores. The company also performed high-resolution whole metagenomics sequencing of stool samples collected from patients in both the SER-109 Phase 1b, as well as the Phase 2 trial as part of this analysis. The analysis indicated that subjects in the open-label Phase 1b study who received a higher dose achieved a significantly greater increase in diversity of commensal spore-former bacteria by 1 week post-treatment, as compared to both Phase 1b and Phase 2 subjects treated with lower doses. These results suggest that the dose used in the SER-109 Phase 2 study may have been suboptimal in certain patients, and may have resulted in a less robust drug effect, contributing to decreased efficacy in Phase 2, as compared to the Phase 1b study.

Much of the SER-109 Phase 2 microbiome-related learnings are based on advancements in the computational analytics and higher resolution whole metagenomics sequencing techniques that Seres is pioneering, and several of these methods were developed after the SER-109 Phase 2 study was designed. Insights obtained from this work may also
benefit Seres’ broad preclinical and clinical microbiome development pipeline.

Analysis of SER-109 Phase 2 Study Clinical Drug Product

The company also conducted a thorough and detailed investigation of the potential impacts of manufacturing and formulation changes implemented in the Phase 2 study. No issues regarding product quality or formulation were identified which would have impacted the Phase 2 study results.

Summary of SER-109 24-Week and Open Label Extension Study Results

The full, 24-week Phase 2 study results continue to demonstrate that SER-109 was generally well tolerated. The most common adverse events associated with SER-109 included diarrhea, abdominal pain and flatulence. The Phase 2 study population represented older individuals, many in poor health, and a high rate of serious adverse events (SAEs) was reported in both study arms. A numerically higher rate of SAEs was observed in the SER-109 arm (15.0% versus 10.3% for placebo), however there was no detectable pattern in the SAEs observed, and none of these were considered to be SER-109 drug-related by the study investigators.

As expected with recurrent C. difficile infection, relatively few additional recurrences occurred beyond 8 weeks, and the 24-week data provides relatively little new information regarding efficacy. Based on 24-week data, five further patients recurred in the SER-109 arm, but three of the five recurrences (60%) were in patients who terminated the trial early, resulting in an imputed recurrence. In the placebo arm, one patient also terminated the trial early, resulting in an imputed recurrence. Early terminations, and loss of patients to follow-up, are common in the long safety follow-up portions of clinical trials.

Phase 2 study subjects who experienced a C. difficile recurrence had the option to enroll in an open label extension study, where they were treated with SER-109 and were followed for an additional 24 weeks. In total, 34 patients entered the open label extension study and 11 patients recurred during the initial 8-week study period, a 32% recurrence rate.

Source:

About Seres Therapeutics:  Seres Therapeutics, Inc. is a leading microbiome therapeutics platform company developing a novel class of biological drugs that are designed to treat disease by restoring the function of a dysbiotic microbiome, where the natural state of bacterial diversity and function is imbalanced. The Phase 2 study of Seres’ program SER-109 has been completed in multiply recurrent C. difficile infection. Seres’ second clinical candidate, SER-287, is being evaluated in a Phase 1b study in patients with mild-to-moderate ulcerative colitis (UC). Seres is also developing SER-262, the first ever synthetic microbiome therapeutic candidate, in a Phase 1b study in patients with primary C. difficile infection. For more information, please visit http://www.serestherapeutics.com. Follow us on Twitter @SeresTx.

Forward-looking Statements:  This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our SER-109 development plans, the timing, design, and potential results of a new clinical study for SER-109, the potential for a redesigned trial to provide different results, and the impact any analysis may have on clinical outcomes.

These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding, which may not be available; our limited operating history; the unpredictable nature of our early stage development efforts for marketable drugs; the unproven approach to therapeutic intervention of our microbiome therapeutics; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; potential delays in enrollment of patients which could affect the receipt of necessary regulatory approvals; potential delays in regulatory approval, which would impact the ability to commercialize our product candidates and affect our ability to generate revenue; any fast track or Breakthrough Therapy designation may not lead to faster development, regulatory approval or marketing approval; our possible inability to receive orphan drug designation should we choose to seek it; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; our lack of experience in manufacturing our product candidates; the potential failure of our product candidates to be accepted on the market by the medical community; our lack of experience selling, marketing and distributing products and our lack of internal capability to do so; failure to compete successfully against other drug companies; potential competition from biosimilars; failure to obtain marketing approval internationally; post-marketing restrictions or withdrawal from the market; anti-kickback, fraud, abuse, and other healthcare laws and regulations exposing us to potential criminal sanctions; recently enacted or future legislation; compliance with environmental, health, and safety laws and regulations; protection of our proprietary technology; protection of the confidentiality of our trade secrets; changes in United States patent law; potential lawsuits for infringement of third-party intellectual property; our patents being found invalid or unenforceable; compliance with patent regulations; claims challenging the inventorship or ownership of our patents and other intellectual property; claims asserting that we or our employees misappropriated a third-party’s intellectual property or otherwise claiming ownership of what we regard as our intellectual property; adequate protection of our trademarks; ability to attract and retain key executives; managing our growth could result in difficulties; risks associated with international operations; potential system failures; the price of our common stock may fluctuate substantially; our executive officers, directors, and principal stockholders have the ability to control all matters submitted to the stockholders; a significant portion of our total outstanding shares are eligible to be sold into the market; unfavorable or lacking analyst research or reports; and we are currently subject to securities class action litigation. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission, or SEC, on November 10, 2016 and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

Reference:

  1. Polage, C. R., et al. (2015). Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era. JAMA Internal Medicine, 175(11), 1792–1801.

IR or PR Contact:

Carlo Tanzi, Ph.D., Seres Therapeutics, 617-203-3467

Head of Investor Relations and Corporate Communications

Ctanzi@serestherapeutics.com

Microbiome – C. diff. Treatments On The Horizon

NewsUpdate

 

 

 

PROBIOTICS:

Pick a disease or disorder, and somebody, somewhere, has said that a probiotic supplement—an over-the-counter, unregulated pill usually filled with a single strain of friendly gut bacteria—might cure it, whether it’s cancer, obsessive-compulsive disorder, or a yeast infection.

But there’s very little evidence that probiotic supplements do any good. “There’s a lot of promise here but not a lot of proof yet,” said Cliff McDonald, associate director for science at the Centers for Disease Control and Prevention’s Division of Healthcare Quality Promotion.

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CDC Reports:

Half a million people a year are infected with C. diff in the U.S., the CDC estimates, with 29,000 annual deaths related to the diarrheic bacterium. More than 65 percent of C. diff infections involve exposure in a health-care facility, according to a 2015 study, creating more than $4.8 billion in excess health-care costs at acute-care facilities alone.

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C. diff. Treatments On The Horizon:

To Learn More About ALL C. diff. Clinical Trials In Progress Click On The Following Link:

https://cdifffoundation.org/clinical-trials-2/

 

Seres Therapeutics, a microbiome-based biopharmaceutical company in Cambridge, Mass., is developing a pill, subject to a rigorous approval process under the Food and Drug Administration, to tackle recurrent Clostridium difficile. (The digestive system’s microbiome is the community of healthy gut bacteria that normally reside in the body.)

Seres aims to put the science behind a proven treatment of recurrent C. diff, fecal transplants, in a pill, which wouldn’t require a colonoscopy. Like probiotic supplements, it’s a gut bacteria product. Unlike the supplements, by the time it’s available it will have gone through the FDA wringer. It will contain about 50 strains of bacteria proven effective in treating C. diff and will require a doctor’s prescription.

Recurrent C. diff is an obvious entry point for Seres, said Chief Executive Officer Roger Pomerantz. “We asked, what is the lowest-hanging fruit?” But it’s hardly the end. The company has built a microbiome library of 14,000 strains of human bacteria it hopes will help it treat a range of diseases, eventually without needing feces at all.   Seres has embarked on the research with some pretty lofty goals, including finding treatments for obesity, liver disease, and cancer. It has partnerships with Massachusetts General Hospital, the Mayo Clinic, Memorial Sloan Kettering Cancer Center, and other respected medical institutions.  “We will figure out exactly what’s wrong with the microbiome, design a drug, and then pull the organisms out with our library, never touching a human donation,” Pomerantz said.    Seres’s lead product candidate, SER-109, will treat recurrent C. diff with four capsules taken orally instead of with transplants. While fecal matter is the raw material for the pills, the final product consists only of the spores necessary to treat the infection, which will have been extracted and purified.  SER-109 is expected to become the first oral microbiome therapy approved by the FDA, though Seres declined to predict exactly when it will arrive. Results from the latest trials are due by midyear, and Phase 3 trials are scheduled to follow later in the year. Seres hopes to follow up quickly with SER-287, a drug to treat ulcerative colitis, which could be the first microbiome drug to treat a chronic disease, and SER-262, to treat primary C. diff before it turns into the recurrent kind.

Other companies are racing to collect enough data for FDA approval, but right now Seres, which is publicly traded, looks to be the one to beat. “Seres is probably going to be the first one that’s going to knock at the FDA’s door,” said Mohan Iyer, chief business officer at Second Genome, a microbiome company studying how to treat disease with the compounds produced by gut bacteria instead of the gut bacteria themselves.

“SER-109 is poised to be first-in-class among fecal microbiota transplant-derived drugs,” Joseph Schwartz, an analyst at Leerink Partners, wrote in a May report. The report says the latest trial results “wowed the Street” but warns that the company could still be held back by “disappointing clinical data” and obstacles in the regulatory process.

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Another top contender is Rebiotix. Its RBX2660 is also designed to treat recurrent C. diff but, unlike SER-109, is administered with an enema; an oral version is in development. The treatment also differs significantly from Seres’s in formulation, including thousands of kinds of microbes from the donor’s stool, compared with SER-109’s 50 or so, as many as could be preserved and some of which haven’t even been identified.

“We make sure we have a minimum concentration of certain kinds that we know the patients lack,” CEO Lee Jones said. “But we don’t identify all of them. There’s no way to do that.” A recent study estimated that 1014 bacteria are in the human gut, most of which have never been isolated. Jones said the drug could hit the market by 2018.

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  • UPDATES:

The medications have been shown to be similarly effective—with no C. diff-associated diarrhea for 29 of 30 of Seres’s patients  and  27 of 31 of Rebiotix’s, in the companies’ latest results—and equally safe. Adverse reactions for both are limited to such problems as moderate diarrhea and abdominal cramping, which could be from the C. diff itself. Both have been designated as “breakthrough therapies” by the FDA, allowing for an expedited approval process, and both are likely soon to provide an at-home alternative to fecal transplants.

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Point Of View:

“I don’t know who is going to make it across the line first,” said Gail Hecht, director of gastroenterology and nutrition at Loyola University Medical Center and chairwoman of the American Gastroenterological Association for Gut Microbiome Research & Education. Hecht has attended a Seres advisory board meeting but doesn’t have a financial interest in the company. “It is indeed a race,” she said.

Seres does have at least one distinct market advantage. “Patients have different preferences,” Hecht observes, but “in general, people don’t particularly like enemas.”

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Human Fecal Transplants:

For nearly two thousand years, doctors have looked to this unlikeliest of places for medicine. One of the earliest documented applications is from the fourth-century Chinese medical doctor Ge Hong, whose “yellow soup” recipe to treat diarrhea included a healthy person’s dried or fermented feces. Sixteen hundred years later, in 1958, patients infected with C. diff received the first known human fecal transplants.

Stool Bank Information: 

Today the effectiveness of fecal transplants (formally known as fecal microbiota transplants) to treat recurrent C. diff is supported by a long list of studies, with researchers attributing the results to the restoration of the microbiome. OpenBiome, a nonprofit stool bank, shipped 1,828 treatments in 2014, a number that ballooned to 7,140 treatments in 2015 and looks to be eclipsed this year, with 4,323 treatments shipped to its clinical partners through May 31. And these numbers don’t take into account the transplants performed through directed fecal donations.

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To read article in its entirety:

http://www.bloomberg.com/news/articles/2016-06-30/coming-soon-gut-bacteria-that-actually-cure-your-disease

Vedanta Biosciences Raised $50 Million With Plans To Advance Precise Cocktails Of Bacteria Into Clinical Testing

vedanta

 

 

 

Vedanta Biosciences of Cambridge, MA, has raised $50 million with plans to take advance a number of drugs—precise cocktails of bacteria—into clinical testing.

Formed by company creator PureTech Health six years ago,

Vedanta is trying to understand the relationship between the microbiome and human disease.

The quest to understand the human microbiome has been picking up steam. In Washington, the Obama administration just launched the $121 million Microbiome Initiative, adding to a string of high-profile initiatives in cancer, brain research, and precision medicine. And microbiome drugs are making their way into testing.

The most advanced candidate, SER-109 from Seres Health, is in mid-stage trials for a dangerous gastrointestinal infection called clostridium difficile (C. diff). Data should come this quarter.

These therapies have several different forms. Enterome and Second Genome are developing small molecule drugs to modify the way bacteria interact with their host’s gut. Synlogic and EnBiotix are genetically engineering bacteria. Vedanta and Seres pack strains of bacteria into a pill.

Other than Seres’s C. difficile treatment and a follow-on drug for ulcerative colitis, all of these efforts are preclinical.

But Vedanta CEO and PureTech vice president Bernat Olle views SER-109 as just the beginning for microbiome drugs.

“Clinically it’s been very successful and it’s helped bring the field a lot of attention that otherwise wouldn’t have been received, but I’ve always seen it as a first generation approach that over time ought to be replaced by more refined approaches,” he says.

Vedanta’s first candidate is VE-202, for inflammatory bowel disease, and should begin its first trial in the first half of next year, according Olle.

Johnson & Johnson, which inked a $339 million licensing deal with Vedanta in 2015, will be in charge of VE-202 development. Vedanta is broadening its efforts into infectious diseases (hospital-acquired infections that can’t be controlled by antibiotics), allergies, and potentially cancer. Everything in its pipeline is made from cocktails of live bacteria.

Olle says Vedanta can expand thanks to a deeper understanding how the immune system and gut microbes interact. Initially the company focused on microbes that might help tamp down immune responses—and thus treat autoimmune diseases like IBD.

But Vedanta has since identified microbes that do the opposite: they help rev up the body’s defenses, perhaps to mount a stronger fight against an infection or respond to cancer. Vedanta is trying to amass a library of these strains, much like a pharma company might have a slew of chemical compounds to screen through. “We’re trying to make this a more rational, controllable type of approach,” Olle says.

The new $50 million infusioncomes from new backers Rock Springs Capital, the microbiome-focused fund Health For Life Capital, and Invesco Asset Management (one of PureTech’s investors). PureTech also participated.

Vedanta recently moved out of Cambridge’s LabCentral incubator and into 9,000 square feet in Cambridge. It’s hired several executives, among them chief scientific officer Bruce Roberts, formerly of Genzyme, and head of manufacturing Dan Couto, recently of Sepracor.

The cash will help Vedanta drive “multiple” programs towards clinical testing, Olle says, boost its manufacturing capability, and double its staff to 30.

To read article in its entirety:

http://www.xconomy.com/boston/2016/06/06/vedanta-nabs-50m-to-expand-microbiome-into-immune-boosting-therapies/#

C Diff Foundation Shares a Community Of Clinical Studies In Progress Focused On Clostridium difficile (C.diff.) Prevention and Treatments Worldwide

Clinical Studies In Progress To Help You — Help Them — Help Others  ♥

Every scientific research and development, every clinical trial in progress is a glimmer of hope………..HOPE for clinically safe and approved avenues to prevent and treat a
C. difficile infection
.

For More Information — Visit The ClinicalTrials.gov Website

https://clinicaltrials.gov/

ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. Learn more About Clinical Studies and About This Site, including relevant History, Policies, and Laws.

 

Listed below you will find information pertaining to organizations who have active clinical trials in progress.  Click on each organization’s website listed to review their clinical trial study opportunities — Inquire if you or your loved one qualify to participate in their study. 


*Please note:  The C Diff Foundation does not endorse any products and/or clinical study in progress. All website postings are strictly for informational purposes only.

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Here is a list of Clinical Trial Phases:

Clinical trials are conducted in a series of steps, called phases – each phase is designed to answer a separate research question.

  • Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
  • Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
  • Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
  • Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations and any side effects associated with long-term use.

Additional Resource Information on clinical trials can be found at http://clinicaltrials.gov/info/resources

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  C. diff. Infection (CDI)_Prevention on the Horizon

SyntheticBiologics2016LOGO

Synthetic Biologics’ SYN-004 Phase 2b Proof-of-Concept Clinical Trial

 A global, multi-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the ability of SYN-004 to degrade certain IV beta-lactam antibiotics within the GI tract to maintain the natural balance of the gut microbiome for the prevention of C. difficile infection, C. difficile associated diarrhea and antibiotic-associated diarrhea in patients hospitalized for a lower respiratory tract infection and receiving IV ceftriaxone.

Click here to see if there’s a study site in the U.S. near you and if you’re eligible.

Click here to learn more about SYN-004.

Updated: 4/14/2016

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On March 1, 2016: Cdiffense Phase III Trial updates discussed with Doctors of Sanofi Pasteur To listen to the Podcast ~ Click on the Sanofi Pasteur Logo below and enjoy listening to the Sanofi Pasteur “Cdiffense” clinical updates.

SANOFI_Pasteur_RVB

Sanofi Pasteur, one of the leading vaccine manufacturers in the world, is in the midst of its Phase III clinical trial called Cdiffense to study its investigational vaccine to prevent Clostridium difficile infection (CDI). The trial is now in more than 20 countries across 5 continents to evaluate the safety, immunogenicity and efficacy of an investigational vaccine for the prevention of primary, symptomatic CDI. The investigational C. diff vaccine is designed to produce an immune response that targets the toxins generated by C. diff bacteria, which can cause inflammation of the gut. The investigative vaccine ultimately may help prevent a future infection from occurring. Volunteers for the study should be age 50 or older and planning an upcoming hospitalization or have had at least two hospital stays and have received systemic antibiotics in the past year. For more information on the Cdiffense trial, please visit www.cdiffense.org

For more information, visit www.cdiffense.org

 WATCH this video to learn more about Clostridium diffiicle and Cdiffense

https://youtu.be/IPunIvOaurA

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DAV-Logo (2)

Da Volterra is a biopharmaceutical company, privately-held and headquartered in Paris (France), focused on the discovery and development of innovative therapeutic and preventive products for Clostridium difficile and multi-resistant infections. Our most advanced product, DAV132, is designed as a prophylactic treatment intended to prevent the development of
C. difficile infection, by binding with and neutralizing common antibiotics in the gut
.
DAV132 decreases the risk of triggering CDI by inactivating residual antibiotics in the colon
before they can disrupt the bacterial flora, without impacting the systemic efficacy of the antibiotics.

It is noteworthy that DAV132 is developed to accompany all oral and intravenous antibiotics of any class and would therefore significantly reduce the risks to acquire C.difficile infections for patients at risk (especially patients who had prior episodes). We see DAV132 as a real game changer for C.difficile prevention.

Have a look at our video presenting the mechanism of action of DAV132:

http://davolterra.com/content/dav132-preventing-occurence-and-recurrence-clostridium-difficile-infections-video

The video is highly illustrative of what C.diff is and how C.diff is triggered.

We have already performed 2 clinical trials with DAV132 and we have a very exciting dataset (both preclinical and clinical) suggesting that DAV132 will very effectively prevent C.diff infections. I would be happy to exchange with you more information on this. Our next clinical trial, in patients actually treated with antibiotics and at-risk of C.diff, will start in Q4 2015 or early 2016.

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Valneva Announces Start of Phase II Clinical Trial of its Clostridium difficile vaccine candidate

  • First Study participant(s) enrolled in Phase II trial which aims to enable Phase III entry upon successful completion
  • Study to enroll 500 healthy subjects aged 50 years and older in the United States and Germany
  • First results are expected in Q4 2015

   Lyon (France), December 18, 2014European biotechnology company Valneva SE (“Valneva”) announced today the initiation of the Phase II clinical trial of its VLA84 prophylactic vaccine candidate against Clostridium difficile (C. difficile), the main cause of nosocomial diarrhea. Data from the Phase I study in healthy elderly and adults showed good safety and immunogenicity of the vaccine candidate, and indicated functionality of induced antibodies, supporting the Company`s decision to progress the vaccine
candidate into Phase II

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C. diff. Infection (CDI) Treatments On the Horizon

Seres Therapeutics is a clinical-stage therapeutics company focused on discovering and developing drugs to treat diseases of the microbiome. The biology of the microbiome is driven by ecologies—the functional collections of various organisms—which are central to health and disease. Seres is developing Ecobiotic® therapeutics to treat diseases where an abnormal (unhealthy) microbiome is a significant factor in the underlying cause of the disease. Our first clinical program, The ECOSPOR Research study is in the treatment of recurrent
Clostridium difficile infection.
About The ECOSPOR Research Study  Although antibiotics are used to treat recurrent
C. difficile infection, most of the time they do not cure C. difficile. In addition, antibiotics continue to wipe out the good bacteria that protect you
against C. difficile. Currently, there are no medications available that can prevent this infection from coming back when your gut is defenseless.

SER-109 is an investigational medicine being developed to prevent recurrent C. difficile from coming back again. The idea is to first treat patients with antibiotics that work against C. difficile so that the diarrhea goes away. Then patients may get SER-109 to keep the C. difficile infection from coming back.

In the ECOSPOR study, doctors will compare SER-109 to a placebo pill, which looks like SER-109. However, the placebo pill will have no medication inside it. Patients will be randomly assigned to receive either SER-109 or placebo. The study is designed to provide more information about the potential safety and effectiveness of SER-109, and will last about 7 months. The results will help doctors and researchers learn whether SER-109 could one day be used to prevent recurrent CDI.

Who Is Eligible For The ECOSPOR Study?
To pre-qualify for this study, a person must:
• Be 18 years of age or older
• Have a history of at least 3 episodes of Clostridium difficile Infection (CDI) in the last 9 months, including the current episode
• Not have active irritable bowel syndrome with diarrhea within the previous 24 months
All study-related visits, tests, and medication will be provided to the study patients at no cost. In addition, reimbursement for time and travel may be provided.

How to Enroll in the study?   The ECOSPOR Study is now open for enrollment. It is posted on ClinicalTrials.gov.All the sites which are enrolling patients are listed on clinicaltrials.gov, including contact information for the sites. If a doctor in the study thinks you may be a good candidate, you will be given complete information about the study including everything you should know before you join.  You can also contact clinicalstudies@sereshealth.com to find a doctor near you who is involved in the study.

To LISTEN to Dr. Shelley Trucksis, Ph.D., M.D., and Dr. David Cook, Ph.D. discuss “Ecobiotics- A Novel Approach to Recurrent C. difficile infections”  Click on the Seres Therapeutics Logo below:

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Seres Therapeutics, a leading microbiome therapeutics company, which recently published in the Journal of Infectious Diseases, positive results from an open-label Phase 1b/2 study of SER-109 for the treatment of patients with recurrent C. difficile infections (CDI). Seres Therapeutics is creating a new class of medicines to treat diseases resulting from functional deficiencies in the microbiome, a condition known as dysbiosis. New insights into the human microbiome are fundamentally reshaping how we understand and treat a wide range of diseases, creating new possibilities for patients not served by current therapeutic approaches. Ecobiotics are ecological compositions of beneficial organisms that are designed to reestablish a healthy microbiome. The discovery efforts at Seres Therapeutics currently span metabolic, inflammatory, and infectious diseases. 2016

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summit

Summit Therapeutics  has reported ‘outstanding’ results in the phase II trial of ridinilazole, its new C.difficile infection (CDI) treatment.

During the trial, the new oral antibiotic significantly outperformed vancomycin, the current standard prescription, which was the primary objective said Summit.

Over two-thirds (66.7%) of those treated showed a sustained clinical response (SCR) against 42.4% for vancomycin.

The statistical superiority was driven by a large numerical reduction in recurrent disease compared with vancomycin, which Summit said was key as recurrence is one of the hardest things to stop.

C.difficile or CDI is a growing danger for patients in hospital, care homes and the wider community.

Annually, there are between 450,000 and 700,000 cases in the US alone, with the elderly and sick especially vulnerable.

One study has suggested it costs US $4.8bn to treat these people.

“The healthcare community is acutely aware of the major threat CDI poses, particularly given widespread antibiotic use and our aging population,” said Glyn Edwards, Summit’s chief executive.

The biggest unmet need in CDI treatment is reduce recurring cases, he added and the results from the latest trial had exceeded its ‘wildest expectations’.

“These outstanding clinical data from CoDIFy strongly support the profile of ridinilazole as a narrow spectrum antibiotic.

“There is a vital need for potent new antibiotics, and the potential of ridinilazole has attracted great interest.

Edwards added that the results from the CoDIFy trial were exceptionally encouraging and the aim no is to advance ridinilazole into Phase 3 clinical trials.

Here, the company would evaluate partnership opportunities against the benefit of it forward itself, he added.

Professor Mark Wilcox, at Leeds University and Public Health England’s lead consultant on C.difficile added that the latest data indicated ridinilazole could become an important new treatment option for CDI with the potential to reduce the high rates of recurrent disease that remain a key clinical challenge.

CoDIFy was a double blind, randomised, active controlled, multicentre, Phase II clinical trial that evaluated the efficacy of ridinilazole against vancomycin in 100 patients in the US and Canada.

Results from a second CoFIFy trail are due next year, though Edwards said the results announced today would provide the bulk of the quantitative data.

ridinilazole has already received Qualified Infectious Disease Product, or QIDP, designation and has been granted Fast Track status from the US Food and Drug Administration

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rebiotixlogo

Rebiotix Inc. is a clinical stage biotechnology company founded to revolutionize the treatment of debilitating diseases by harnessing the power of the human microbiome. Microbiota Restoration Therapy (MRT) is the company’s platform for delivering live microbes into a sick patient’s intestinal tract to treat disease.

Clinical Program
PUNCH™ CD is the name of Rebiotix’s clinical program to assess the safety and efficacy of RBX2660 for the treatment of recurrent Clostridium difficile (C. diff.) infection. It is the most advanced human clinical program evaluating a microbiota-based drug conducted in coordination with the U.S. Food and Drug Administration (FDA) with the goal of developing and commercializing a new therapy to treat patients with recurrent episodes of C. diff. infection. Rebiotix has completed enrollment its PUNCH CD 2 study and continues to assess the safety and efficacy of RBX2660.

PUNCH™ CD 2
Rebiotix has completed enrollment in its PUNCH CD 2 study, a Phase 2B multi-center, randomized, double-blind, placebo-controlled trial to evaluate RBX2660 for the treatment of recurrent C. diff. infection. A total of 117 patients recruited at more than 20 sites in the U.S. and Canada were enrolled in the study, which is the largest randomized controlled study of a MRT for recurrent C. diff. to date.

In this study, the patients received either the microbiota-based drug or a placebo via enema. Neither the doctor nor the patients knew what treatment was received in order to get an unbiased measurement of the drug’s true effectiveness. If a patient’s C. diff. infection symptoms returned, even if they were in the placebo arm of the study, they may have been eligible to receive RBX2660. This is referred to as the open-label portion of the study.

PUNCH™ CD
The PUNCH CD study, which was a Phase 2 open label safety and preliminary efficacy study of RBX2660, was successfully completed in July 2014. An open label study means everyone enrolled in the study got the treatment and it is generally the first phase of a new product development program. The study demonstrated a success rate of 87% for those treated with no serious adverse events related to either the product or the method of delivery.

Product Pipeline
Rebiotix is currently exploring the feasibility of an oral formulation, RBX7455, for the prevention of C. diff.

In addition, Rebiotix is leveraging their years of knowledge and experience to develop MRT applications for other conditions that result from disruption of the gut microbiota.

For more information on Rebiotix and the PUNCH CD and PUNCH CD 2 studies go to:
http://www.rebiotix.com or clinicaltrials.gov.

Caution: Drug products are in development and investigational at this time. No product has yet been approved by the U.S. Food and Drug Administration.

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Merck & Co. will file the first antibacterial monoclonal antibody by the end of 2015, the company says.

bezlotoxumab was successful in two Phase III trials against the recurrence of

Clostridium difficile (C. difficile) infection when combined with antibiotics.

Merck plans to file new drug applications for the monoclonal antibody in the US, Canada and EU by the end of the year. Currently, there are no therapies approved for the prevention of recurrent disease caused by C. difficile.

Bezlotoxumab’s approval would also make it the first antibody to treat bacterial infection.

Scientists say mAbs would have benefits over small molecule antibiotics because they are less likely to drive antimicrobial resistance and are administered less frequently. “Results of these studies showed that a single, one-time infusion of the antitoxin bezlotoxumab given with standard of care C. difficile antibiotic treatment significantly reduced the recurrence of C. difficile infection compared to standard of care alone, and demonstrated this benefit over a 12-week period,” said lead investigator Mark Wilcox of the University of Leeds, UK. “These results were also demonstrated in patient subgroups known to be at high risk for C. difficile recurrence.”

C. difficile toxin B can damage the gut wall and cause inflammation, leading to the symptoms of C. difficile enteritis, which include abdominal pain and watery diarrhea. Bezlotoxumab, a fully-human monoclonal antibody, was developed by researchers at the University of Massachusetts Medical School’s MassBiologics Laboratory with Medarex (now part of Bristol-Myers Squibb), and licensed to Merck in 2009.

The studies   Merck’s studies took more than 1,000 patients each and evaluated them over 12 weeks. Participants received either a single infusion of bezlotoxumab, actoxumab (another mAb designed to fight C. difficile),a combination of the two, or a placebo. The actoxumab arm of the study ended early for efficacy and safety reasons.    Both studies had infection recurrence as their primary endpoint – this rate was significantly lower for the bezlotoxumab arms (17.4% and 15.7%) and bezlotoxumab plus actoxumab arms (15.9% and 14.9%), compared to placebos (27.6% and 25.7%). Actoxumab was found not to provide extra benefit on its own or combined with bezlotoxumab, so Merck’s marketing authorisation application is for bezlotoxumab alone.

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To Listen to the Podcast — MERCK’s Dr. Nicholas Kartsonis discusses the many contributions of Merck and ongoing research addressing CDI  — and  the history in addressing infectious disease and antimicrobial resistance. Dr. Nick Kartsonis also  discusses the future in the area of C. diff. and some of the company’s current treatments, including DIFICID and their ongoing research addressing CDI  Click on the MERCK Logo Above *

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DIFICID (fidaxomicin) is currently FDA approved to treat Clostridium difficile-associated diarrhea (CDAD) in adult patients 18 years of age and older.

Currently, clinical trials are ongoing to assess the efficacy and safety of DIFICID, in either a tablet and oral suspension formulation, in pediatric patients with CDAD.  **  In addition, DIFICID is currently in clinical trials to determine the efficacy of use as a prophylaxis against CDAD in adult patients undergoing hematopoietic stem cell transplantation (HSCT).

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XBiotech is a biotech company located in Austin, Texas and was founded on the concept of the “True Human Antibody”.  Antibodies are specialized proteins, which are produced by the immune system.  Their function is to bind to a very specific target, such as a virus or bacteria, and aid in the elimination of these targets by the immune system.  Monoclonal antibodies were developed as a class of drug, which use the specific targeting function of the antibody to target substances that cause disease. Currently approved monoclonal antibodies however, are developed in the laboratory or in mice.  XBiotech’s approach is to isolate antibodies that are present naturally in healthy human donors, and develop these into products that can be used to treat disease.  We believe that antibodies isolated from humans, will be safer and will function better than so called antibodies marketed as “fully human”, which are in fact engineered.

Over the past decade, Clostridium difficile (C. diff) has emerged as a significant public health threat.  In fact, the CDC has designated it as an “Urgent threat level.”

In October 2015, XBiotech announced it had set out to develop a first-in-class oral monoclonal antibody against C. diff infection. Just two weeks after this announcement, the Company reported it had already identified positive blood samples for anti-clostridium difficile antibodies after screening blood donations from healthy volunteers.

XBiotech’s plans to develop an antibody therapy that directly targets and neutralizes the bacteria. The Company intends to deliver the therapy orally, targeting C. diff in the gastrointestinal tract, where the antibody could reduce the bacteria’s ability to establish debilitating or life threatening infections.

XBiotech

Click on the XBiotech LOGO to the left  to listen to the February 2016  XBiotech Podcast which introduces XBiotech, developer of True Human(TM) therapeutic antibodies. XBiotech has an exciting pipeline of product candidates in various areas of medicine. The Company recently announced the launch of a research and development program to develop a first-in-class oral monoclonal antibody against Clostridium difficile (C.difficile) infection. The Company will discuss the need for an effective C.difficile therapy, their novel approach to treating the disease as well as efficiency in their manufacturing technology. Join guests: Dr. Michael Stecher, Medical Director, Dr. Sushma Shivaswamy, Vice President of Research and Development, and Kelly Thornburg, Senior Vice President of Operations, as they discuss how XBiotech is pioneering a new era in the discovery and development of targeted antibodies therapeutics.

For more information please contact the Company by emailing info@xbiotech.com or calling 512-386-2900.    www.xbiotech.com

Highlights — 4th Annual International “Raising C. diff. Awareness” Conference — Boston

symposium

THE C DIFF FOUNDATION 

  4th ANNUAL

INTERNATIONAL RAISING C. diff. AWARENESS CONFERENCE

HIGHLIGHTS — PROMISE & CHALLENGES IN C. diff.  TREATMENT

Part 1: Novel Approaches and Therapies in Development

The Centers for Disease Control first recognized C. difficile infection (CDI) as an urgent threat to public health in September 2013. However, I first began to understand the impact on patients in 2008 when I was first diagnosed with Clostridium difficile (C. diff).  My journeys, including many months of illness (nine recurrent CDI) which  included a referral to hospice care before finally being correctly treated in 2009.  Henceforth; I was no stranger to this diagnosis with over two decades of  Nursing and witnessing the loss of my Father, whose life was claimed by C. difficile involvement in 2004.

C. diff.  has left me with serious health complications. Though I returned to my career as a Nurse for a brief time, I was diagnosed with an entirely new  C. diff infection in 2011– enduring  nine recurrences through the following year.  Another year  taken away from C. diff..

Like many other patients, the physical, financial and emotional toll has been great – not only on me, but also on my family.  Yet, through my  journeys and what I have learned in the process has inspired me to help others affected by C. diff.  and share with fellow healthcare professionals through educating and advocating for C. difficile infection prevention, treatments, and environmental safety worldwide.

I was proud to kick off the third annual International Raising C. diff Awareness Conference & Health EXPO in Cambridge, MA last fall.   The Annual Conference is one of many important initiatives the C Diff Foundation undertakes to build awareness, advance advocacy and support research to address the public health threat posed by this devastating, life-threatening  infection and common healthcare-associated infection.

Through the Conference–  the C Diff Foundation offers perspective from world renowned experts on C. difficile infection prevention, treatment and research, with discussions ranging from pharmaceutical options to environmental safety products.

♦ Here are the  highlights from our guest speakers ♦

Bezlotoxumab

Dr. Mary Beth Dorr, Director of Clinical Research, Infectious Diseases at Merck, presented the most recent data on the company’s C. diff antitoxin, bezlotoxumab. Nearest to potential FDA approval among new options for patients, bezlotoxumab would be used as an adjunct to standard antibiotic regimens for C. diff, with a goal of reducing recurrences—something for which no other drug has been approved.

Merck’s first trial, MODIFY 1 (Monoclonal Antibodies For C. DIFficile Therapy), included 1,412 patients globally. In addition to standard treatment of care, patients received a single intravenous infusion of either the antitoxin actoxumab (binds to the C. diff toxin A) or bezlotoxumab (binds to the C. diff toxin B) alone, or the two in combination, or a placebo.

This study called for a pre-specified interim analysis allowing for modifications in the trial after 40% of patients had completed a 12-week follow-up. As a result, actoxumab alone was dropped from further study as it did not provide added efficacy over bezlotoxumab alone or the combination of bezlotoxumab and actoxumab.

The MODIFY 2 trial evaluated an additional 1,163 patients who received standard antibiotic treatment for C. diff plus either bezlotoxumab alone, or the combination of bezlotoxumab and actoxumab, or placebo. The primary endpoint was prevention of a recurrence of C. diff infection at 12 weeks defined as a new episode of diarrhea and a positive stool test for toxigenic C. diff.

Many of the patients in the trial were quite ill: 17% had severe CDI, 18% had the more virulent PCR ribotype 027 strain, and about 20% were immunocompromised.

For the two studies overall, the rates of recurrent C. diff were significantly less in patients receiving bezlotoxumab alone than placebo (17% vs. 28%). Adverse events were no different in the treatment and placebo groups.

Because there was no benefit to the combination of the two antibodies, bezlotoxumab alone was selected for new drug applications submitted to the US FDA and European Medicines Agency seeking marketing approval.

Ecobiotics  — A Novel Approach To Recurrent CDI’s

Fecal microbial therapy, also referred to as FMT or stool transplants, generated much discussion. However; this therapeutic approach aiming to change the gut microbiome, the collection of bacteria and other microorganisms in and on our bodies, is being studied in clinical trials by two of the presenters.

Dr. David Cook, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Seres Therapeutics, spoke about “ecobiotic therapeutic restoration.” He noted that a dysbiotic, or imbalanced microbiome, is increasingly linked to multiple diseases including C. difficile infection, inflammatory bowel disease, and metabolic diseases like diabetes mellitus.   ECOSPOR ™ is their current Phase 2 clinical study focused on the safety and efficacy of SER-109, a drug for the potential prevention of recurrent Clostridium difficile infection (CDI) in adults who have had three or more episode of CDI within the previous nine months.

In its Phase 2 study, Seres used spores from the Clostridiales group of organisms, treated to decrease the risk of any pathogen transmission. A small group of patients with > 3 prior CDIs were given two doses of a mixture of strains of spores by mouth and followed up for 8 weeks. In this study, 13 of 15 (87%) patients met the primary endpoint of no recurrent diarrhea associated with a positive test for C. diff.

Another study, using a slightly smaller dose of spores, had the same findings. Overall, 29 of 30 (97%) patients had clinical resolution of their diarrhea; the improvement persisted at 24 weeks. A slightly larger Phase 2 study is underway now and Phase 3 studies are planned for 2016. The drug has received breakthrough and orphan drug designations from the FDA. Seres’ drug also reduced carriage of or colonization by multi-drug resistant organisms (MDRO), including Klebsiella, Providencia, and Vancomycin-resistant enterococci (VRE), all of which are recognized by the CDC as urgent or emerging health threats.

RBX2660  —  Therapeutic Microbiota Restoration

Dr. Lee Jones, Foundress and CEO of Rebiotix, presented ongoing studies with RBX2660. Their product, RBX2660, which also aims to restore a gut microbiome altered by CDI, has been designated a drug, rather than a tissue transplant, by the FDA and has received fast track, orphan drug, and breakthrough therapy designations. The liquid microbial suspension packaged for enema delivery is manufactured differently than fecal microbial transplants, and the end-product is standardized and ready for administration.

The initial Phase 2 study, PUNCH™, was open-label and included 30 patients with at least two recurrences of C. diff requiring hospitalization. With a 6-month follow-up period, this trial had an 87% efficacy rate and no recurrences. A second 120 patient randomized, placebo-controlled, double-blind trial (PUNCH CD 2) is ongoing. Rebiotix is also developing an oral formulation and planning trials for other indications.

Vaccines

Approaches to vaccination were also discussed at the conference by the companies leading those research initiatives. Mucosal vaccination, to protect people from pathogens that enter or cause harm at the mucosal surface, or lining of our gastrointestinal or respiratory tracts, has been used in developing a variety of vaccines, including polio, typhoid, and experimental influenza vaccinations. Dr. Simon Cutting, PhD, Professor of Molecular Microbiology at
Royal Holloway, University of London
, explained the rationale behind this approach and reviewed supporting animal data. If approved, this vaccine would be administered orally.
These studies are still in early development.

Dr. Patricia Pietrobon, Associate Vice President, Research and Development, C. diff Program Leader at Sanofi Pasteur, presented an update on the company’s vaccine, H-030-012, which relies on injection of an inactivated whole toxin to both C. diff toxins A and B. Sanofi’s vaccine showed immunogenicity in patients in Phase 2 studies, and was the first vaccine to be awarded fast track approval by the FDA. Their vaccine showed an antibody response and immunologic boost after a dose at 6 months, suggesting vaccination might confer long-term protection from C. diff. A 15,000 participant, 5-year, global trial is underway, hoping to provide long-term immunity to C. diff.

Several other approaches for C. diff prevention and treatment were presented:
The first, described by Dr. Klaus Gottleib, MD, FACG, Vice President, Clinical Development and Regulatory Affairs, Synthetic Biologics, involves use of a beta-lactamase enzyme given orally in combination with a patient receiving a beta-lactam (penicillin or cephalosporin) antibiotic. The antibiotics would still have full efficacy in the blood or soft tissue, but the company’s hypothesis is that the enzyme will destroy unneeded antibiotic in the gut and will prevent
C. diff from developing by reducing alteration in the gut flora.
Their drug, SYN-004, is in Phase 2 trial development.

Dr. Martha Clokie, Ph.D.  Leicester UK, Professor in Microbiology.  Dr. Cloakie’s research focuses on phages that infect bacterial pathogens of medical relevance and  is focusing on  targeting  C. diff without altering the rest of the microbiome in preclinical studies. Hoping to destroy
C. diff with a biological warfare approach, she focuses on phages, tiny virus-like particles that infect bacteria.

Dr. Melanie Thompson, Ph.D.  is studying an older drug used for rheumatoid arthritis, auranofin, in Australia. Auranofin targets the selenium metabolism of C. diff, and is likely to be fairly specific treatment against that bacterium.

 

Part 2 – Challenges in Testing and Infection Management

 

Challenges

Testing

Among the key presentations, Dr. Mark Wilcox, MD, FRCPath, Head of Microbiology and Academic Lead of Pathology at the Leeds Teaching Hospitals, Professor of Medical Microbiology at the University of Leeds, lead on Clostridium difficile for Public Health England, and Chairman of the conference, addressed the challenges of diagnosing C. diff..  From knowing who to test, to which test to employ, the state of testing poses challenges in accurately determining the number of CDI cases and in comparing rates over time or between locations.

He raised important questions for the medical community to address:

  •  Who should be tested?
  • Which tests should be used?
  • How do we measure accuracy between tests in order to compare infection rates over time and by location?

Dr. Wilcox showed data from the Euclid Study in Europe looking at approximately 4,000 stool samples submitted to participating hospital labs on a given day, whether or not a test for           C. diff. was ordered.  The data shows that about 25% of cases were missed by the hospitals, but were picked up by a centralized reference lab.  On a single day, 246 patients (6.3%) received an incorrect result from their hospital.  The translates to about 40,000 cases of CDI missed in Europe alone per year and underscoring that CDI is far more common, and commonly missed than appreciated, making it hard to grasp both the magnitude of the problem and the treat individual patients.

Barley Chironda, RPN, CIC, Manager of Infection Prevention and Medical Device Reprocessing at St. Joseph’s Health Centre, Toronto, Ontario, Canada also addressed the topic of testing in acknowledging that some physicians may also be reluctant to order C. diff. tests both because the tests can be hard to interpret, and because there may be perceived disincentives for detecting and reporting the infection .  Hospitals can be penalized financially for infections acquired in the hospital as well as receive lower quality of care ratings.

Antibiotic Stewardship

While there is confusion over how to test for C. diff. there is a general understanding as to what we must do to contain the epidemic — use fewer antibiotics.  Currently, up to 85% of patients with C. difficile associated diarrhea (CDAD) have received antibiotics in the 28 days before their CDI occurred.  More than 1/2 of all hospital patients receive an antibiotic, as do almost all surgical patients.  Estimates are that 30 – 50% of antibiotic use is unnecessary or inappropriate.

As Dr. Hudson Garrett, Jr., PhD, MSN, MPH, FNP, CSRN, VA-BC, Vice President, Clinical Affairs, PDI, Nice-Pak, and Sani Professional, explained, education of both healthcare workers and patients is needed.  Prescribers need to limit antibiotic use to the most specific or narrowest spectrum antibiotic they can, and patients need to learn that antibiotics are not helpful for colds or viral infections.

If use of broad-spectrum antibiotics in hospitals is reduced by 30%, the CDC has estimated there will be 26% fewer CDI’s.  Garrett stressed the importance of good leadership and multidisciplinary approach to the success of an antibiotic stewardship program, emphasizing the need for engagement, education and involvement from the top administrators, physicians, pharmacists, and patients,

Another concern is the overuse of the class of antibiotics called quinolones.  An especially toxic and severe strain of C. diff. NAP2/027/B1 has been emerging, seemingly driven by the use of fluoroquinolone antibiotics.  Quinolones are a widely prescribed class of antibiotics often used in treating pneumonia.

Limiting antibiotics and more appropriate use is not just for people — it is also important in agriculture.  There is a growing concern that contaminated products — both meat and                 produce — may transmit resistant organisms to people and spread C. diff. outside healthcare facilities.

Infection Control

Controlling the spread of  C. diff.  is a challenge.  While previously believed to be strictly a             healthcare-associated infection, recent findings show that many patients acquire C. diff. in the community.

As part of his presentation, “Behind the Scenes;  C. difficile Management in Health from the lens of an Infection Preventionist, ”  Barley Chronda, also reviewed infection control issues, focusing on the importance of cleaning.  He noted that 11% of occupants in a hospital room would acquire C. diff. if a prior patient had the infection.

The issues hospitals face include:

  •  A lack of dedicated equipment which may allow for the spread of C. diff. spores on items like stethoscopes and blood pressure cuffs;
  • Isolation for patients with diarrhea or incontinence with consideration for patient symptoms, hospital costs and appropriate patient care;
  • Lack of clarity re: responsibility for cleaning specific items, and what type of cleaning agent to use, as many products do not inactivate spores.  Clorox ® and UV-C Xenon, a high-energy, full spectrum ™ pulsed Xenon Ultraviolet Light by Xenex — both sponsors of the Conference, were addressed as options for CDI and a variety of multi-drug resistant organisms.
  • Hand-washing (Hand Hygiene) as many hospitals lack conveniently placed sinks and rely on alcohol hand sanitize gels and solutions,.  While alcohol is great for reducing most bacterial contamination, it is ineffective against C. diff. spores.

The Patient Journey Continues

Nancy Sheridan an Educator and  Volunteer Patient Advocate, represented the voice of the many patients who face the challenges of being diagnosed,  treated, and surviving a C. diff.  infection and shared her experience with the audience.  After developing diverticulitis complicated by a perforated colon following an overseas trip.  Nancy was treated with antibiotics and developed diarrhea.  Though doctors thought she might have a travel – related infection, she insisted on being tested for C. diff. and found C. diff. was causing her severe symptoms.  She suffered recurrent C. diff. infections, forcing her to take a leave of absence from her job.  In addition to the loss of income and mounting medical bills, she described feeling “defeated and broken.”

Desperate, housebound, in pain, and having a marked weight loss from her recurrent vomiting and bloody diarrhea, she asked for a fecal transplant.  Despite multiple refusals, she persisted.  Eight months after her ordeal began, Nancy received the stool transplant.  She describes her recovery as “miraculous” and within a few weeks, she was back to her teaching and active life.  Nancy concluded her story by reminding us that on any given day, 1 of 25 hospitalized patients becomes infected with C. diff. noting “the risk of contracting this deadly infection is too  great to remain uninformed.”

That message – from Nancy Sheridan, from the professionals who support us, and the patients who we hear from each day on our U.S. national Hot-Line (1-844-FOR-CDIF) continue to drive us in educating, and advocating for C. diff. infection prevention, treatments, environmental safety, and providing support worldwide.

About The C Diff Foundation
The C Diff Foundation is a leading non-profit organization founded in 2012 by Nancy Caralla, a Nurse who was diagnosed and treated for recurrent Clostridium difficile (C. difficile) infections. Through her own journey, and the loss of her father to C. difficile infection involvement, Nancy recognized the need for greater awareness through education about research being conducted by the government, industry and academia and better advocacy on behalf of patients, healthcare professionals and researchers worldwide working to address the public health threat posed by this devastating infection. Follow the C Diff Foundation on Twitter (@cdiffFoundation) or Facebook. For more information, visit: http://www.cdifffoundation.org/.