Tag Archives: OpenBiome

The American Gastroenterological Association (AGA) Fecal Microbiota Transplantation (FMT) National Registry Enrolls First Patient

Largest planned fecal microbiota transplantation (FMT) study enrolls first patient

The FMT National Registry also announces collaborations with American Gut and OpenBiome

The first participant has enrolled in the American Gastroenterological Association (AGA) Fecal Microbiota Transplantation (FMT) National Registry, which is planned to be the largest FMT study ever.

The AGA FMT National Registry — funded by the National Institutes of Health (NIH) and administered by the AGA Center for Gut Microbiome Research and Educationwill track 4,000 patients for 10 years after their FMT procedure, providing a wealth of data about the procedure’s effectiveness and both short- and long-term effects of FMT.

Fecal microbiota transplant is a medical procedure in which the stool from a healthy person is prepared and then put into the intestine of a sick patient. FMT is most commonly used to treat Clostridium difficile (C. diff) infection, if antibiotics have not been able to get rid of the infection.

“Today is an important milestone for the AGA FMT National Registry. What’s ahead is a significant repository of data for investigators working to advance FMT research, better information for physicians on when and how to use FMT, and reassurance for patients that we now understand the risks and benefits of this procedure,” said Gary D. Wu, MD, a principal investigator for the registry and founding chair of the AGA Center for Gut Microbiome Research and Education scientific advisory board. “We look forward to embarking on this comprehensive data collection project and are eager to share our findings with the public.”

First Patient Enrolled

The first patient enrolled in the FMT National Registry received a fecal transplant through the Gastroenterology Center of Connecticut/Medical Research Center of Connecticut by Paul Feuerstadt, MD, assistant clinical professor of medicine at Yale School of Medicine, New Haven, CT. The patient being treated had experienced multiple recurrences of C. difficile infection. As part of the registry,

Dr. Feuerstadt will follow up with the patient four times over the next two years and report back on the patient’s health post-FMT. The patient will also provide yearly reports for up to 10 years.

How Patients Can Take Part in the FMT National Registry

AGA expects 75 sites to be included in this registry. Visit ClinicalTrials.Gov <https://clinicaltrials.gov/ct2/show/study/NCT03325855?cond=FMT+National+registry&rank=1> on a regular basis to track new sites added to the registry. Patients should reach out to their health care provider to discuss participation in the registry.

Patients should first review AGA’s patient information on fecal microbiota transplantation (FMT) <http://www.gastro.org/info_for_patients/clostridium-difficile-106-fmt-details>.

UC San Diego to Build FMT National Registry Biobank

AGA is collaborating with the American Gut Project — an academic effort run by the laboratory of Rob Knight, PhD, professor and director of the Center for Microbiome Innovation at the University of California, San Diego — to build a biobank of stool samples from participants in the FMT National Registry. American Gut will receive stool samples from registry participants before and after their FMT. The microbiota will be sequenced in each sample, and remaining material will be frozen to be made available for future research. Eventually, this information could help doctors screen and select the best donor samples for individual patients.

OpenBiome Joins as a Registry Collaborator

AGA is also collaborating with OpenBiome, a public stool bank and nonprofit research organization that provides clinicians with rigorously screened, ready-to-use stool preparations for fecal transplant procedures. As the only public stool bank in the country, OpenBiome serves as the source of stool preparations for nearly 1,000 clinical partners performing FMT across the United States. For patients enrolled in the registry who receive OpenBiome FMT material, OpenBiome will provide screening information and samples to support the registry’s research analyses.

To read this article in its full entity, please click on the following link to be redirected:

https://www.eurekalert.org/pub_releases/2018-01/aga-lpf010918.php

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

Fecal Transplants (FMT) Treating Clostridium difficile Infections; U.S. Food and Drug Administration (FDA) Seeks Comment on What Investigational New Drug (IND) Requirements To Waive

Fecal Transplants to Treat C. difficile: FDA Seeks Comment on What IND Requirements to Waive

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The US Food and Drug Administration (FDA) on Monday February 29, 2016,announced new draft guidance that aims to further assure that patients infected with the bacterium Clostridium difficile and not responding to standard therapies can access poop transplants, also known as fecal microbiota for transplantation (FMT).

FDA considers FMT an investigational new drug (IND), which requires physicians and scientists to file an IND application if they intend to use the treatment for clinical practice or research.

However, FDA has issued guidance stating that FMT may be used to treat 

C. difficile infection not responsive to standard therapies outside of a clinical trial. 

New Guidance

The latest draft guidance offers new notice that FDA intends to exercise enforcement discretion regarding the IND requirements for the use of FMT to treat C. difficile infection.

As far as what FDA wants to discuss on this new draft guidance, the agency says it’s requesting comments on which IND requirements are appropriate to waive.

In particular, FDA is requesting comments on the requirement for institutional review board review of the use of FMT to treat patients with C. difficile infection not responding to standard therapies when the FMT is provided by a stool bank,” FDA says.

Background

The draft guidance comes as over the past few years, FMT, which basically involves the transfer of a healthy donor stool to the bowel of a patient infected with C. difficile, has emerged as an effective means to treat recurrent forms of the bacterial infections, according to a study in the Journal of Law and Biosciences.

Rachel Sachs, an academic fellow at Harvard University’s Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics, and an author of that study, explained to Focus that previously FDA said it would regulate FMT like a biologic, but that the decentralized, hospital-based model of FMT envisioned in this new draft guidance more closely resembles the agency’s models for regulating tissue or cord blood products.

Two companies – Rebiotix and Seres Therapeutics – have been granted orphan drug designations for their INDs as FMT treatments for recurrent C. difficile infections, which affect between 85,000 and 110,000 people in the US annually.

And Sachs said she’s under the assumption that once a company gets FDA approval for their FMT product, FDA will revoke its enforcement discretion included in this new guidance.

Guidance Details

FDA said Monday it intends to use this discretion for waiving certain IND requirements, provided that:

  • The licensed health care provider treating the patient obtains consent from the patient or his or her legally authorized representative for the use of FMT products. The consent should include, at a minimum, a statement that the use of FMT products to treat C. difficile is investigational and a discussion of its reasonably foreseeable risks;
  • The FMT product is not obtained from a stool bank; and
  • The stool donor and stool are qualified by screening and testing performed under the direction of the licensed health care provider for the purpose of providing the FMT product for treatment of the patient.

And FDA makes clear that an establishment that collects or prepares FMT products “solely under the direction of licensed health care providers for the purpose of treating their patients (e.g., a hospital laboratory) is not considered to be a stool bank under this guidance.”

Sachs co-authored her article with Carolyn Edelstein, director of policy and global partnerships at OpenBiome, a nonprofit stool bank that sells FMT capsules (recommended dose of 30 capsules plus a safety test capsule costs $535, or stool preparations for delivery by colonoscopy, enema, and EGD/naso-enteric tube are $385 each) after conducting first-in-human evaluations (N=4) and a randomized dose-finding study (N=17).

Edelstein told Focus that the draft “suggests that the FDA is seeking to set up a more tailored regulatory scheme, one that considers stool banking separately from small-scale directed donation. We are in favor of seeing stool banking receive more regulatory oversight. We plan to answer the agency’s request for comments on the elements of a regulatory framework that would lend this oversight to the practice of stool banking without unduly burdening the physicians and healthcare facilities using banked material, and by extension, unduly limiting access to the treatment for their patients.”

FDA also explains that there were “difficulties in interpretation” with previous draft guidance, particularly around the provision that the donor be known either to the patient or to the treating licensed health care provider, noting “the revised approach more accurately reflects our intent to mitigate risk, based on the number of patients exposed to a particular donor or manufacturing practice rather than the risk inherent from any one donor.”

But as new FMTs are likely to hit the market as orphan drugs, the bigger issue at play could be associated with cost. Sachs noted that any FDA-approved treatment, particularly since it’s an orphan product, could be expensive (upwards of thousands of dollars for treatment).

 

Source:

http://www.raps.org/Regulatory-Focus/News/2016/02/29/24428/Fecal-Transplants-to-Treat-C-difficile-FDA-Seeks-Comment-on-What-IND-Requirements-to-Waive/

Comparison Study Shows Efficacy in Frozen Fecal Product To Fresh For Fecal Microbiota Transplantation To Treat Recurrent C. diff. Infections

Frozen fecal microbiota transplantation showed efficacy comparable to fresh FMT for clinical resolution of diarrhea among adult patients with recurrent or refractory Clostridium difficile infection, according to results of a randomized trial published in JAMA.

Using frozen FMT would reduce costs associated with donor screening frequency, provide immediate availability of the treatment and enable delivery of the treatment to centers without on-site laboratory facilities,

the researchers wrote. “Previous studies have supported the use of frozen FMT for management of recurrent [C. difficile infection] but have not directly compared frozen with fresh FMT.”

Lee CH, et al. JAMA. 2016;doi:10.1001/jama.2015.18098

Malani PN, Rao K. JAMA. 2016;doi:10.1001/jama.2015.18100

Christine H. Lee, MD, from McMaster University in Canada, and colleagues, conducted a double-blind, noninferiority trial involving 232 adult patients with recurrent or refractory C. difficile infection (CDI) at six Canadian academic medical centers from July 2012 to September 2014. Patients were randomly assigned to receive frozen (n = 114) or fresh (n = 118) FMT via enema without bowel preparation, and if they showed no improvement by day 4, they received an additional FMT between days 5 and 8.

No recurrence of CDI-related diarrhea at 13 weeks and adverse events served as primary outcomes, and a 15% margin was set to confirm noninferiority.

In the per-protocol population (frozen, n = 91; fresh, n = 87), 83.5% of the frozen FMT group achieved clinical resolution compared with 85.1% of the fresh FMT group, a difference of – 1.6% (95% CI, – 10.5% to ∞; P = .01 for noninferiority). In the modified intention-to-treat population (frozen, n = 108; fresh, n = 111), 75% of the frozen FMT group achieved clinical resolution compared with 70.3% of the fresh FMT group, a difference of 4.7% (95% CI, – 5.2% to ∞; P < .001 for noninferiority). Adverse and serious adverse events were comparable between groups; the most common adverse events were transient diarrhea (70%), abdominal cramps (10%) or nausea (< 5%) during the 24 hours after FMT, and constipation (20%) and excess flatulence (25%) during follow-up, all mild to moderate in severity.

“Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea,” the researchers concluded. “Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting.”

These researchers have provided

“the best evidence to date supporting the use of frozen stool, with their finding that use of frozen stool for FMT resulted in a rate of clinical resolution of diarrhea that was no worse than that obtained with fresh stool for FMT and will likely expand the availability of FMT for patients with recurrent CDI,”

Preeti N. Malani, MD, MSJ, associate editor of JAMA, and Krishna Rao, MD, MS, both from the University of Michigan Health System, Ann Arbor, wrote in a related editorial. “The ability to use frozen stool eliminates many of the logistical burdens inherent to FMT, because stool collection and processing need not be tied to the procedure date and time.

This study also provides greater support for the practice of using centralized stool banks, which could further remove barriers to FMT by making available to clinicians safe, screened stool that can be shipped and stored frozen and thawed for use as needed. In theory, procedure costs may also be decreased, since comprehensive donor screening is expensive.” – by Adam Leitenberger

Disclosures: Lee reports she has participated in clinical trials for ViroPharma, Actelion, Cubist and Merck, and served as a member of the advisory boards for Rebiotix and Merck. Please see the study for a full list of all other researchers’ relevant financial disclosures. Malani and Rao report no relevant financial disclosures.dR

TO READ ARTICLE IN ITS ENTIRETY CLICK ON LINK BELOW:

http://www.healio.com/gastroenterology/infection/news/online/%7Bbac5a422-a30c-4501-8e35-05e9a346772a%7D/frozen-fmt-noninferior-to-fresh-fmt-for-treating-recurrent-c-difficile-infection

UBiome and OpenBiome Partner in Microbiome Studies

The study will provide new insights on mechanics of fecal microbiota transplantation with patients being treated for a C. diff. infection.

uBiome and OpenBiome Partner for Microbiome Study in FMT Patients

Study will provide new insights on mechanics of fecal microbiota transplantation in patients treated for a C. difficile infection.

uBiome and OpenBiome announced a new partnership to study the microbiome of patients undergoing fecal microbiota transplantation (FMT) as a treatment for Clostridium difficile infections (C. diff).

Any patient undergoing clinical FMT treatment can request their complimentary mail-order microbiome testing kit at http://ubiome.com/pages/fmt. The kit allows them to swab a sample of their microbiome, which they send back to uBiome for analysis and sequencing. uBiome will use the collected data to conduct a study of FMT’s impact on the body’s microbiota. All study participants will also receive a detailed report on their personal microbiome.

“Because we will be looking at patients before, during, and after FMT we will be able to learn about how the microbiota adjusts to the treatment,” adds OpenBiome Co-Founder and President Dr. Mark Smith. “This has the potential to not only shed light on C. diff, but also open the door to using FMT with patients suffering other conditions.”

C. diff infections can occur when there is a severe imbalance of gut microbiota. Because of this imbalance, the bacterium thrives and causes extreme gastrointestinal distress.

This study will serve to increase awareness and understanding of how FMT affects the human microbiome, which could increase its acceptance in the medical community as a way to treat a potential variety of gastrointestinal conditions.

About uBiome:
uBiome (ubiome.com) sequences the microbiome for citizen scientists, researchers, and clinicians, using microbial genomics to help patients benefit from new discoveries in scientific research. uBiome conducts research studies on the microbiome and develops clinical diagnostics based on microbiome research.

About OpenBiome:
OpenBiome (openbiome.org) is a nonprofit stool bank dedicated to expanding safe access to fecal microbiota transplantation (FMT) therapies. Founded by a team of microbiologists, public health advocates, and concerned citizens, OpenBiome aims to significantly reduce the practical barriers for clinicians providing FMTs, while connecting scientists across studies and disciplines.

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

http://www.prweb.com/releases/2015/07/prweb12820941.htm

June 2015

Nation’s First Fecal Transplant Stool Sample Bank Opens

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Grad students at MIT have created and started the Nation’s first stool sample bank.

“Enter OpenBiome, which provides $250 samples to hospitals from screened patients, and has sent more than 135 such “preparations” to 13 hospitals since September; the samples are currently exclusively used for the treatment of C. diff.

For additional information on OpenBiome, please click on this link to their website.   http://www.openbiome.org/

What does OpenBiome do?

We work with clinicians to make FMT easier, cheaper, safer and more widely available. We do so by providing hospitals with screened, filtered, and frozen material ready for clinical use. This service eliminates the time, staff, protocols, and facilities needed to screen and prepare material from new donors for each treatment. With OpenBiome, all that’s needed to deliver FMT is a doctor and an endoscope.

To read the “Nation’s first ‘poop bank’ article, please click on the following link:

http://www.foxnews.com/health/2014/02/20/nations-first-poop-bank-opens-to-provide-stool-samples-for-fecal-transplants/?fb_action_ids=745159872170649&fb_action_types=og.likes&fb_source=other_multiline&action_object_map=%5B279077495590268%5D&action_type_map=%5B%22og.likes%22%5D&action_ref_map=%5B%5D