Tag Archives: Recurrent C. difficile Infection Clinical Trials

Seres Therapeutics SER-109 Met Phase 3 Primary Endpoint, Positive Results From Pivotal Phase 3 ECOSPOR III Study Evaluating Investigational Oral Microbiome Therapeutic For Recurrent C. difficile Infection

– SER-109 met Phase 3 primary endpoint, showing a highly statistically significant 30.2% absolute reduction in the rate of C. difficile infection recurrence compared to placebo 

– SER-109 was well tolerated, with a safety profile comparable to placebo 

– Efficacy results substantially exceeded FDA regulatory guidance to support BLA filing as a single pivotal trial; Company to meet with the agency to discuss filing for product approval as soon as possible 

 Positive SER-109 Phase 3 data provide validation for Seres’ microbiome therapeutics platform and further development of its pipeline of product candidates 

 Seres Therapeutics, Inc. reported on August 10, 2020, positive topline results from the pivotal Phase 3 ECOSPOR III study evaluating its investigational oral microbiome therapeutic SER-109 for recurrent C. difficile infection (CDI). The study showed that SER-109 administration resulted in a highly statistically significant absolute decrease of 30.2% in the proportion of patients who experienced a recurrence in CDI within eight weeks of administration versus placebo, the study’s primary endpoint. 11.1% of patients administered SER-109 experienced a CDI recurrence, versus 41.3% of placebo patients. The study results were equally compelling when characterized by the alternative metric of sustained clinical response, where 88.9% of patients in the SER-109 arm achieved this objective.

The study’s efficacy results exceeded the statistical threshold previously provided in consultation with the U.S. Food and Drug Administration (FDA) that could allow this single clinical study to fulfill efficacy requirements for a Biologics License Application (BLA). The SER-109 safety results were favorable, with an adverse event profile comparable to placebo.

“We are extremely pleased with these highly clinically meaningful SER-109 Phase 3 study results, greatly exceeding the statistical threshold provided by the FDA. Based on our prior discussions with the FDA, we believe this trial should provide the efficacy basis for submitting an application for product approval. We look forward to meeting with the FDA as soon as possible to discuss the regulatory path forward with the goal of bringing SER-109 to patients as a first-in-class microbiome therapeutic,” said Eric D. Shaff, President and Chief Executive Officer of Seres. “Our results represent the first-ever positive pivotal clinical study results for a targeted microbiome drug candidate. We believe these Phase 3 data provide strong validation for our underlying microbiome therapeutics platform, which has been the scientific basis for the Company, as well as persuasive clinical evidence supporting our other active pipeline programs.”

“We would like to thank all those who participated in this landmark study. Based on these highly positive SER-109 ECOSPOR III results, we believe that this novel microbiome therapeutic candidate could potentially provide a much-needed effective oral treatment option for the approximately 170,000 patients in the U.S. that suffer from recurrent CDI annually,” said Lisa von Moltke, M.D., FCP, Chief Medical Officer of Seres. “Seres applied a data-driven and scientifically rigorous approach to develop SER-109. The proprietary scientific learnings we have obtained continue to drive our overall R&D efforts and the advancement of our other ongoing microbiome therapeutic programs.”

“Recurrent C. difficile infection is a serious disease that devastates patients’ quality of life, and in many severe cases may result in a patient’s death. Today’s treatment options have important shortcomings related to efficacy, safety and route of administration, and novel approaches that target the root causes of the disease are urgently needed. The SER-109 Phase 3 results are highly impressive and represent an exceptional advance in the fight against this disease. I believe that SER-109 has the potential to fundamentally transform the treatment of recurrent C. difficile infection,” said Mark Wilcox, M.D., Professor of Medical Microbiology, University of Leeds.

ECOSPOR III Study Design and Results

The ECOSPOR III study (ClinicalTrials.gov identifier: NCT03183128) is a multicenter, randomized, placebo-controlled study that enrolled 182 patients with multiply recurrent CDI. Patients were randomized 1:1 to receive either SER-109 or placebo, after standard of care antibiotic treatment. SER-109, or placebo, was administered orally for three consecutive days. All patients were required to have a positive C. difficile toxin diagnostic test both at study entry and in the case of suspected recurrence to ensure the selection of individuals with active disease and to confirm the accuracy of the primary endpoint.

The primary efficacy endpoint of ECOSPOR III was the proportion of patients with recurrent CDI at up to eight weeks following administration of SER-109 or placebo. As a secondary endpoint, patients are evaluated for CDI recurrence through 24 weeks post-treatment, and the Company plans to present those results at a future date.

SER-109 met the study’s primary endpoint with a significantly lower recurrence rate of 11.1% in SER-109 patients versus 41.3% in placebo patients at eight weeks; p<0.001 tested at the one-sided 0.25 level. Patients administered SER-109 experienced a 30.2% lower rate of recurrence, on an absolute basis, compared to placebo. The SER-109 treatment arm relative risk was 0.27 (95% CI=0.15 to 0.51) versus placebo. The ECOSPOR III recurrence rates translate into a sustained clinical response rate of 88.9% versus 58.7% with SER-109 and placebo, respectively. The SER-109 Number Needed to Treat (NNT) was approximately 3.

In prior discussions, the FDA communicated that demonstration of a statistically very persuasive efficacy finding in the ECOSPOR III primary endpoint, defined as demonstrating a 95% upper confidence level of relative risk lower than 0.833, could support a BLA submission on the basis of this single study. The results of ECOSPOR III demonstrated a SER-109 relative risk of 0.27 (95% CI=0.15 to 0.51) compared to placebo. As a result, Seres believes that this study should support the efficacy basis for BLA submission. SER-109 has obtained FDA Breakthrough Therapy and Orphan Drug designations.

SER-109 was well tolerated, with no treatment-related serious adverse events (SAEs) observed in the active arm, and an adverse event profile similar to placebo. The overall incidence of patients who experienced AEs during the eight-week study period was similar between SER-109 and placebo arms. The most commonly observed treatment-related AEs were flatulence, abdominal distention and abdominal pain, which were generally mild to moderate in nature, and these were observed at a similar rate in both the SER-109 and placebo arms.

A SER-109 open-label study is ongoing ( clinicaltrials.gov identifier: NCT03183141) at selected clinical sites that participated in the ECOSPOR III study, and the Company may initiate the program at additional clinical sites. The FDA has previously indicated that SER-109 administration to at least 300 patients, consistent with standard FDA guidance, would be required to support BLA submission. The ongoing SER-109 open-label study is continuing to contribute to the SER-109 safety database.

The Company plans to immediately request a Breakthrough Therapy designation meeting with the FDA to discuss the requirements to submit a BLA seeking regulatory approval of SER-109. Given the favorable efficacy and safety results seen in ECOSPOR III, the safety results observed in prior SER-109 clinical studies, and the critical unmet need for a therapeutic option for recurrent CDI patients, the Company plans to discuss with the FDA the safety data requirements for a BLA filing.

Seres continues to advance its commercial readiness for the potential launch of SER-109. In June 2020, Seres appointed Terri Young, Ph.D., R.Ph., as Chief Commercial and Strategy Officer. The Company has been conducting activities to support successful future potential commercialization. Seres believes that the commercial opportunity for SER-109 could be substantial, given the dire need for an effective, safe, oral therapeutic, and the strength of the SER-109 Phase 3 study results.

Conference Call Information

Seres’ management will host a conference call today, August 10, 2020, at 8:30 a.m. ET. To access the conference call, please dial 844-277-9450 (domestic) or 336-525-7139 (international) and reference the conference ID number 3216859. Accompanying slides will be posted on the Seres website ahead of the conference call. To join the live webcast, and to view the accompanying slides, please visit the “Investors and Media” section of the Seres website at www.serestherapeutics.com.

A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for approximately 21 days.

About SER-109

SER-109 is an investigational, oral, biologically-derived microbiome therapeutic that is designed to reduce recurrence of C. difficile infection (CDI), enabling patients to achieve a sustained clinical response by breaking the vicious cycle of CDI recurrence and restoring the diversity of the gastrointestinal microbiome. SER-109 is a consortium of purified bacterial spores of multiple Firmicute species, manufactured by fractionating targeted bacteria from the stool of healthy human donors with further steps to inactivate potential pathogens. The FDA has granted SER-109 Breakthrough Therapy designation and Orphan Drug designation for the treatment of CDI.

SER-109 is fundamentally distinct from fecal microbiota transplantation (FMT). SER-109 is comprised of a highly-purified consortia of spore-based commensal bacteria and designed to be manufactured in accordance with Good Manufacturing Practice conditions using stringent standards to ensure product quality and consistency. To support product safety, Seres utilizes a unique manufacturing process that inactivates numerous potential pathogens, including species of non-spore bacteria, such as Escherichia coli, and viruses such as SARS-CoV-2.

About C. difficile Infection (CDI) and Current Treatments

C. difficile infection (CDI) is one of the top three most urgent antibiotic-resistant bacterial threats in the U.S., according to the Centers for Disease Control, and is a leading cause of hospital-acquired infection in the U.S. It is responsible for the deaths of approximately 20,000 Americans each year. CDI is associated with debilitating diarrhea, which significantly impacts quality of life in every functional domain. Since the discovery of C. difficile more than four decades ago, vancomycin has been the most commonly used drug for patient management. Current approaches provide only modest improvements in sustained clinical response rates, leaving behind a significant pool of patients with recurrent disease. Unapproved FMT, used in cases that are not responsive to approved drugs, remains poorly characterized clinically and has been associated with serious safety concerns, including the transmission of bacterial pathogens and the potential transmission of viruses such as SARS-CoV-2, the virus that causes COVID-19. The recent quarantine and shipping hold of FMT from a major stool bank highlights the urgent need for an approved effective and safe treatment for recurrent CDI.

About Seres Therapeutics

Seres Therapeutics, Inc., (Nasdaq: MCRB) is a leading microbiome therapeutics platform company developing a novel class of multifunctional bacterial consortia that are designed to functionally interact with host cells and tissues to treat disease. Seres’ SER-109 program achieved the first-ever positive pivotal clinical results for a targeted microbiome drug candidate and has obtained Breakthrough Therapy and Orphan Drug designations from the FDA. The SER-109 program is being advanced for the treatment of recurrent C. difficile infection and has the potential to become a first-in-class FDA-approved microbiome therapeutic. Seres’ SER-287 program has obtained Fast Track and Orphan Drug designations from the FDA and is being evaluated in a Phase 2b study in patients with active mild-to-moderate ulcerative colitis. Seres is developing SER-401 in a Phase 1b study in patients with metastatic melanoma, SER-301 for ulcerative colitis and SER-155 to prevent mortality due to gastrointestinal infections, bacteremia, and graft versus host disease. For more information, please visit www.serestherapeutics.com

SOURCE: Seres Therapeutics

Inquire and Consider Becoming A Candidate In a C. difficile Infection Clinical Trial 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
.

 

 

Listed below you will find a web link that will redirect you to obtain information that pertains to organizations who have on-going
C. difficile Prevention and Treatment clinical trials in progress.  

Click on each organization’s website link to review their research and clinical trial study opportunities — Inquire if you or your loved one qualify to participate in a study. Please direct all clinical trial questions to the companies offering the clinical trials.  Thank you.

To Learn More About Clinical Trials —

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.  Click on the link below to be redirected to the clinicaltrials.gov website:

https://clinicaltrials.gov/

 

Clinical Studies In Progress To

Help You — Help Them — Help Others  ♥

 

 

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

 

To review C. difficile Clinical Trials Available Today, please click on the following link to be redirected:

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

 

 

 

 

DISCLAIMER
“The C Diff Foundation’s mission is to educate and advocate for Clostridium difficile infection prevention, treatments, support, and environmental safety worldwide.
The C Diff Foundation’s organization is comprised of 100% volunteering members who are dedicated to our mission and adhere to the Foundation’s Code of Ethics
which prohibits paid endorsements and/or paid promotion of products, services, medications, or clinical studies in progress.   All website postings are strictly for
information purposes.
All website entries, public presentations, and workshops are to raise C. diff. infection awareness in all areas of the C Diff Foundation’s mission statement, including infection prevention, diagnostics, sepsis, healthcare-associated infections, antimicrobial resistance, antibiotic stewardship and provide education on all the above.”

Rebiotix Reports Topline Results From a Controlled Open-label Phase 2 Trial of RBX2660 (PUNCH™ Open Label) For the Prevention of Recurrent Clostridium difficile (C. diff.) Infection (rCDI)

In The News

April 2017

 

 

Rebiotix Inc., a clinical-stage microbiome company focused on harnessing the power of the human microbiome to treat challenging diseases, today announced topline results from a controlled open-label Phase 2 trial of RBX2660 (PUNCH™ Open Label) for the prevention of recurrent Clostridium difficile (C. diff.) infection.

Data indicated that RBX2660 was well-tolerated and achieved the primary efficacy endpoint of preventing C. diff. recurrence; patients treated with RBX2660 exhibited a treatment success rate of 78.8% compared with a historical control of 51.8% (p<0.0001). RBX2660 is a broad-spectrum microbiota suspension that is designed to rehabilitate the human microbiome by delivering live microbes into a patient’s intestinal tract to treat disease.

Lee Jones, president and CEO of Rebiotix, stated, “The 78.8% treatment success achieved in this open label Phase 2 trial demonstrates the potential of RBX2660, a broad spectrum microbiota drug product, to rehabilitate the gut microbiome and break the cycle of C. diff. recurrence. These results, coupled with the safety and efficacy data observed in our prior Phase 2b and Phase 2 clinical trials, position Rebiotix to advance RBX2660 into Phase 3 clinical development, solidifying our standing as the most clinically advanced microbiome company in the industry.”

PUNCH™ Open Label was designed as a prospective, multicenter, open-label, controlled Phase 2 study to assess the efficacy and safety of RBX2660 for the prevention of recurrent C. diff.

The primary efficacy endpoint involved a comparison of patients treated with RBX2660 to a closely matched set of antibiotic only treated historical controls through 56 days. There were 31 active treatment sites and four control sites in the US and Canada. 132 RBX2660 and 110 historical control subjects were included in this topline analysis.

Actively treated patients, after determining eligibility, were administered two doses of RBX2660; the first at day one and the second at day seven. Patients were then monitored for eight weeks to determine whether there was a recurrence of C. diff.

Top line results from the trial, which examined responses from 132 patients versus a historical control of 110 patients, indicated a treatment success rate of 78.8% as compared to a historical control of 51.8% (p<0.0001). Overall, RBX2660 was generally well-tolerated with the most commonly reported adverse events being gastrointestinal, including diarrhea, abdominal pain, flatulence, constipation and distension.


About Rebiotix Inc.

Rebiotix Inc. is a clinical-stage microbiome company focused on harnessing the power of the human microbiome to revolutionize the treatment of challenging diseases. Rebiotix is the most clinically advanced microbiome company in the industry, with its lead drug candidate, RBX2660, expected to enter Phase 3 clinical development for the prevention of recurrent Clostridium difficile (C. diff.) infection. Previously, RBX2660 was the subject of three Phase 2 trials in recurrent C. diff, including a Phase 2b randomized, double-blind, placebo-controlled trial (PUNCH™ CD2), with data indicating the drug was well-tolerated and demonstrated statistically significant treatment efficacy. RBX2660 has been granted Orphan Drug status, Fast Track status and Breakthrough Therapy Designation from the FDA for its potential to prevent recurrent C. diff. infection.

Rebiotix’s development pipeline includes multiple formulations targeting several disease indications and is built around its pioneering Microbiota Restoration Therapy (MRT) platform. MRT is a standardized, stabilized drug technology that is designed to rehabilitate the human microbiome by delivering a broad spectrum of live microbes into a patient’s intestinal tract via a ready-to-use and easy-to-administer format.

For More Information About C. difficile Clinical Trials In Progress : 

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

 

For more information on Rebiotix and its pipeline of human microbiome-directed therapies, visit www.rebiotix.com

 

Source:  Rebiotix 4/17

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

U.S. Panel To the Food and Drug Administration Voted 10-5 In Favor For Merck & Co. ‘s bezlotoxumab Effective At Preventing A Recurrence Of C. diff. Infection

NewsUpdate

 Merck & Co’s experimental drug to treat the most common hospital-associated infectious diarrhea
* Clostridium difficile  *  warrants approval, an advisory panel to the U.S. Food and Drug Administration said on Thursday.

 

The panel voted 10-5, with one abstention, that the drug, bezlotoxumab, was effective in preventing a recurrence of infection with Clostridium difficile, or C. difficile, a germ that causes inflammation of the colon and potentially fatal diarrhea.

The FDA is not obliged to follow the advice of its advisory panels but typically does.

The panel’s vote follows an internal review by FDA staff which found an apparent decrease in recurrence of C. difficile but expressed concern as to whether the drug could hurt the cure rate of the initial C. difficile episode.

Panelists who voted in favor of the drug acknowledged the FDA’s concerns but said they were persuaded there was a need for new targeted therapies and this one seems effective.

“We haven’t had a new drug for C. difficile in our armamentarium for some time,” Dr. Joanna Schaenman, assistant professor of medicine at UCLA David Geffen School of Medicine, said.

MORE about bezlotoxumab :   https://cdifffoundation.org/category/clinical-trials/

Merck & Co.   bezlotoxumab was successful in two Phase III trials against the recurrence of

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

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.

The FDA is due to make its decision by July 23.

 

TO READ ARTICLE IN ITS ENTIRETY CLICK ON THE LINK BELOW:

http://www.channelnewsasia.com/news/health/us-regulatory-panel-backs/2860152.html