Tag Archives: Bezlotoxumab

Study Assessed Bezlotoxumab Cost Effectiveness Added To Standard of Care to Prevent rCDI In High-risk Patients From the Spanish National Health System

Abstract

Introduction

Clostridium difficile infection (CDI) is the major cause of infectious nosocomial diarrhoea and is associated with considerable morbidity, mortality and economic impact. Bezlotoxumab administered in combination with standard of care (SoC) antibiotic therapy prevents recurrent CDI.

This study assessed the cost-effectiveness of bezlotoxumab added to SoC, compared to SoC alone, to prevent the recurrence of CDI in high-risk patients from the Spanish National Health System perspective.

Methods

A Markov model was used to simulate the natural history of CDI over a lifetime horizon in five populations of patients at high risk of CDI recurrence according to MODIFY trials: (1) ≥ 65 years old; (2) severe CDI; (3) immunocompromised; (4) ≥ 1 CDI episode in the previous 6 months; and (5) ≥ 65 years old and with ≥ 1 CDI episode in the previous 6 months. The incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed.

Results

In all patient populations (from 1 to 5), bezlotoxumab added to SoC reduced CDI recurrence compared to SoC alone by 26.4, 19.5, 21.2, 26.6 and 39.7%, respectively. The resulting ICERs for the respective subgroups were €12,724, €17,495, €9545, €7386, and €4378. The model parameters with highest impact on the ICER were recurrence rate (first), mortality, and utility values. The probability that bezlotoxumab was cost-effective at a willingness-to-pay threshold of €21,000/QALY was 85.5%, 54.1%, 86.0%, 94.5%, 99.6%, respectively.

Conclusion

The results suggest that bezlotoxumab added to SoC compared to SoC alone is a cost-effective treatment to prevent the recurrence of CDI in high-risk patients. The influence of changes in model parameters on DSA results was higher in patients  ≥ 65 years old, with severe CDI and immunocompromised. Additionally, PSA estimated that the probability of cost-effectiveness exceeded 85% in most subgroups.

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

https://link.springer.com/article/10.1007/s12325-018-0813-y

Zinplava has been launched by MSD in the UK

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

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

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

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

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

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

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

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

 

ZINPLAVA (bezlotoxumab) Is Now Available For Prescription To Reduce Recurrence Of Clostridium difficile Infection (CDI)

MERCKBW2015_medLogoBLK [Converted] (2)

ZINPLAVA (bezlotoxumab) is now available for prescription.

Ordering information is available on the brand website:

http://www.zinplava.com/

What is Zinplava™ ?

ZINPLAVA™ is indicated to reduce recurrence of Clostridium difficile infection (CDI) in patients 18 years of age or older who are receiving antibacterial drug treatment of CDI and are at a high risk for CDI recurrence.

ZINPLAVA is not indicated for the treatment of CDI.

ZINPLAVA is not an antibacterial drug.

ZINPLAVA should only be used in conjunction with antibacterial drug treatment of CDI.

Full prescribing information can be read at

http://www.merck.com/product/usa/pi_circulars/z/zinplava/zinplava_pi.pdf

The Merck Access Program can help answer physician’s questions about:
Insurance coverage for patients
Prior Authorizations and Appeals
Coding and Billing
Potential financial assistance options for eligible patients

Full program details can be found at:

https://www.merckaccessprogram-zinplava.com/hcp/

Also, Information about co-pay assistance for eligible, privately insured patients
Information about available independent assistance foundation support.

 

*PLEASE NOTE – The C Diff Foundation does not endorse any product, medication,  and/or clinical study in progress and available.     All website postings are strictly for informational purposes only.

 

Recurrent Clostridium difficile (C.diff.) Bezlotoxumab For the Prevention of Recurrent CDI

newsspeaker

Abstract Published: 2017 Jan 26

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.

 

Recurrent Clostridium difficile Prevention

Wilcox MH1, Gerding DN1, Poxton IR1, Kelly C1, Nathan R1, Birch T1, Cornely OA1, Rahav G1, Bouza E1, Lee C1, Jenkin G1, Jensen W1, Kim YS1, Yoshida J1, Gabryelski L1, Pedley A1, Eves K1, Tipping R1, Guris D1, Kartsonis N1, Dorr MB1; MODIFY I and MODIFY II Investigators.
Author information
Abstract

Background Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy.

Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively.

Methods –  We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis.

The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population.

Results In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, -9.9 percentage points; 95% CI, -15.5 to -4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, -11.6 percentage points; 95% CI, -17.4 to -5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, -10.7 percentage points; 95% CI, -16.4 to -5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome.

The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively.

The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea.

Conclusions Among participants receiving antibiotic treatment for primary or recurrent
C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo.

The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239 .).
Also Resource:

https://www.ncbi.nlm.nih.gov/pubmed/28121498

Bezlotoxumab – A New Agent for Clostridium difficile Infection. [N Engl J Med. 2017]

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

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.

……………………………………………………………….

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

♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦♦

  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

………………………………………………………………………

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

—————————————————————

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.

————————————————————–

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

…………………………………………………………………..

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:

seres-therapeutics-inc-logo

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

…………………………………………………………………………………………………………………………………

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

……………………………………………………………………………………………………….

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.

……………………………………………………………………………………………………………………………………

MERCKBW2015_medLogoBLK [Converted] (2)

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.

MERCK2015_Logo_3282_2f432 (2)

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 *

………………………………………………………………………………………………………………………………………

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).

…………………………………………………………………………………………………………………………………….

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/.