Tag Archives: C. diff biological

C. difficile Prevention Clinical Trials; Synthetic Biologics Announces Positive Results from Phase 1a of SYN-004

In the news:

Synthetic Biologics Announces Positive Topline Results from Phase 1a Trial of SYN-004 for the Prevention of                C. difficile Infection

Synthetic Biologics, Inc.  a developer of pathogen-specific therapies for serious infections and diseases, with a focus on protecting the microbiome, announced positive top-line safety and tolerability results from a Phase 1a clinical trial of SYN-004, the Company’s investigational oral beta-lactamase enzyme for the prevention of Clostridium difficile (C. difficile) infection, antibiotic-associated diarrhea and secondary antibiotic-resistant infections in patients receiving intravenous (IV) beta-lactam antibiotic therapy.

Since December 2nd, 2014 the randomized double-blind, placebo-controlled Phase 1a clinical trial conducted at Clinical Pharmacology of Miami, has enrolled 24 healthy volunteers in three cohorts of eight patients each. A total of 18 volunteers have been administered one dose of SYN-004 at increasing dose levels by cohort, and six volunteers received placebo. No clinically significant or relevant adverse events have been reported to date.

“Completing the first safety review and reporting positive top-line results in the Phase 1a clinical trial of SYN-004 is an important event for Synthetic Biologics, bringing us closer to the first potential point-of-care preventative therapy for C. difficile, the CDC’s top-ranking public health threat. Achieving this milestone moves us closer to validating our ground-breaking approach to preventing C. difficile infection in a way that protects the gut microbiome, which also holds the hope of treating a variety of GI, metabolic and CNS disorders,” said Jeffrey Riley, Chief Executive Officer of Synthetic Biologics.

Mr. Riley added, “Based on the results observed in the first three cohorts, and per our clinical plan, we intend to proceed with our planned multiple-ascending dose placebo-controlled Phase 1b study of SYN-004, in which healthy volunteers will receive increasing doses of SYN-004 over several days. We expect enrollment into our Phase 1b SYN-004 clinical trial to begin before year-end, with top-line data available during the first quarter of 2015. We also expect to initiate enrollment in a Phase 2 SYN-004 clinical trial ahead of schedule during the first quarter of 2015.”

SYN-004 is Synthetic Biologics’ oral drug candidate designed to be the first and only treatment intended to prevent C. difficile infection. Its mechanism of action is to bind with and neutralize certain common IV beta-lactam antibiotics in the gut.

During 2012, 14.4 million U.S. patients received approximately 117.6 million doses of IV antibiotics  [i]   that could be inactivated in the gastrointestinal (GI) tract by SYN-004.

SYN-004 is intended to block the unintended harmful effects of antibiotics within the GI tract, maintaining the natural balance of the bacterial flora (gut microbiome), potentially preventing the 1.1 million C. difficile infections[ii] and 30,000 C.difficile related deaths[iii] in the United States each year.

The U.S. Centers for Disease Control (CDC) has identified C. difficile as an “urgent public health threat” and occurs mostly in people who have had recent medical care with IV antibiotics. These antibiotics can create a harmful imbalance in the gut microbiome by killing “good” bacteria, giving C. difficile a chance to multiply and cause diarrhea, which can lead to dehydration, fever, abdominal pain, cramping, nausea, colitis, and even death. In all, 24 million Americans receive IV antibiotics annually  [iv].


[i] This information is an estimate derived from the use of information under license from the following IMS Health Incorporated information service: CDM Hospital database for full year 2012. IMS expressly reserves all rights, including rights of copying, distribution and republication.

[ii] This information is an estimate derived from the use of information under license from the following IMS Health Incorporated information service: CDM Hospital database for full year 2012. IMS expressly reserves all rights, including rights of copying, distribution and republication.

[iii] U.S. Department of Health & Human Services. Agency for Healthcare Research and Quality. January 25, 2012. http://www.ahrq.gov/news/nn/nn012512.htm Accessed: September 30, 2013.

[iv]  This information is an estimate derived from the use of information under license from the following IMS Health Incorporated information service: CDM Hospital database for full year 2012. IMS expressly reserves all rights, including rights of copying, distribution and republication.

SOURCE Synthetic Biologics, Inc.

For further information: Synthetic Biologics:

Kris Maly, VP, Corporate Communication, (734) 332-7800, info@syntheticbiologics.com

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*Please note – The C Diff Foundation does not endorse this product or any product and this posting is strictly for informational purposes only.

Seeking Prevention/Treatment of Clostridium difficile Infection (CDI)

Biologic Research & Development
Seeking Prevention/Treatment of Clostridium difficile Infection (CDI)

As the name implies, biologics are medical agents (such as proteins, cells, or DNA) derived from biological sources used to prevent or treat disease. With advances in biotechnology, biotherapeutic agents are being investigated and/or developed to treat various medical conditions, including:
• Diabetes (human recombinant insulin)
• Anemia (human recombinant erythropoietin)
• Breast Cancer (trastuzumab, monoclonal antibody)
• Cutaneous T-Cell Lymphoma (denileukin difitox, bio-engineered protein)
• CDI (multiple biologics)
• Pertussis/whooping cough (monoclonal antibody)
• Rheumatoid Arthritis (multiple biologics)
• Psoriatic Arthritis (multiple biologics)
• Psoriasis (multiple biologics)

Extensive biologic R&D resources are directed toward preventing/treating CDI. These biologic agents can be described as either biopharmaceuticals, prebiotics or probiotics/live biotherapeutics.

Created by biological process, rather than chemical synthesis, biopharmaceuticals, are medicinal products for the treatment, prevention, or cure of disease in humans. Biologics are generally derived from living material, i.e. microorganisms or cell culture. This is a significant contrast to chemically synthesized small molecule drugs that have a defined, and clearly characterized structure. Types of biopharmaceuticals include:
• Vaccines
• Monoclonal antibodies
• Therapeutic enzymes

Prebiotics are a special type of naturally-occurring fiber that facilitates growth of beneficial (protective) bacteria already living in the colon; they promote an environment that is inhospitable to harmful bacteria. They are found in whole grains, garlic, onions, banana, artichokes and honey. Commercially available prebiotic fiber supplements are commonly used to insure sufficient fiber is ingested to promote a healthy colonic environment.
Probiotics / Live Biotherapeutics
The FDA describes probiotics as live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Probiotics are live microbes (bacteria or yeast) and can be regulated in the United States as both foods and drugs. Examples of probiotics classified as food are dietary supplements and yogurts.

The FDA classifies probiotics as “Live Biotherapeutics” when intended and/or marketed for disease prevention or treatment (probiotics for clinical use); they would require the FDA approval process that is required for drugs and biopharmaceuticals. Even though there have been some promising reports from probiotic biotherapeutic research, strong scientific evidence to support therapeutic use is not available. Currently, the FDA has not approved probiotics for any therapeutic claims.

Biopharmaceutical R&D Projects Seeking CDI Prevention/Treatment
• Vaccine to prevent CDI – Clostridium difficile toxoid vaccine
• Monoclonal antibody combination to prevent recurrent CDI
o Neutralize Clostridium difficile Toxin A and Toxin B
• Beta-lactamase enzyme to prevent CDI following parenteral beta-lactam therapy in hospitalized patients
• Live biotherapeutics to prevent CDI recurrence
o non-toxigenic Clostridium difficile spores in oral dose
o fecal microbiota transplantation
o defined compositions of fecal bacteria


April  2014

Brian Andresen, Chairperson of Biologic Research and Development Committee   (*)              *Michael Kaleko, MD, PhD, Senior Vice President, Reseaerch & Development Synthetic Biologics  *Joseph Sliman, MD, MPH, Senior Vice President, Clinical & Regulatory Affairs, Synthetic Biolgics *Andy Bristol, PhD, Vice President, Research & Development, Synthetic Biologics                   *Lewis Barrett, Senior Vice President, Commercial Strategy, Synthetic Biologics