A research consortium across multiple institutions has begun enrolling patients in a clinical trial examining whether fecal microbiota transplantation by enema is safe and effective in preventing recurrent Clostridium difficile-associated disease, according to a press release.
The researchers hope to enroll 162 volunteers aged 18 years or older who have had two or more episodes of C. difficile-associated disease (CDAD) within the past 6 months, according to the release.
Trial sites include Emory University, Duke University Medical Center and Vanderbilt University Medical Center.
Each site is a member of the Vaccine and Treatment Evaluation Unit, which is a network funded by the National Institute of Allergy and Infectious Diseases (NIAID).
The researchers hope to enroll 162 volunteers aged 18 years or older who have had two or more episodes of C. difficile-associated disease (CDAD) within the past 6 months, according to the release.
“Clostridium difficile-associated disease, a significant problem in health care facilities, causes an estimated 15,000 deaths in the United States each year,” Anthony S. Fauci, MD, NIAID director, said in the release. “This randomized, controlled trial aims to provide critical data on the efficacy and long-term safety of using fecal microbiota transplants by enema to cure C. diff infections.”
Volunteers will be enrolled in the trial after completing a standard course of antibiotics for a recurrent CDAD episode, presuming their diarrhea symptoms cease on treatment.
Participants will then be randomly assigned to either a group (n = 108) that will take an anti-diarrheal medication and receive a stool transplant (FMT) delivered by retention enema, or a group (n = 54) that will take an anti-diarrheal medication and receive a placebo solution delivered by retention enema.
The placebo is a saline solution that has been colored to mimic an active stool transplant product, to ensure that the study is partially blinded.
Researchers will collect stool and blood samples from participating at designated intervals for a year from the date of effective treatment for CDAD, or from the date of their last treatment if it was unsuccessful, according to the release.
Investigators will evaluate the stool samples for gut microbial diversity and infectious pathogens changes and will examine the blood samples for metabolic syndrome markers.
All participants will be monitored for adverse side effects for 3 years following the completion of recurrent CDAD treatment.
CutisPharma Announces FDA Approval Of FIRVANQ™ For Treatment Of Clostridium Difficile Associated Diarrhea (CDAD) And Staphylococcus Aureus Colitis
FDA-approved vancomycin oral liquid therapy expected to improve patient access and reduce pharmacist burden by no longer having to compound liquid formulations
CutisPharma announced today, January 29, 2018, that the US Food and Drug Administration (FDA) has approved FIRVANQ™ (vancomycin hydrochloride) for oral solution, for the treatment of Clostridium difficile associated diarrhea and enterocolitis caused by Staphylococcus aureus, including methicillin-resistant strains.
“We are pleased to announce the FDA approval of FIRVANQ,” said Neal I. Muni, MD, MSPH, Chief Executive Officer of CutisPharma. “FIRVANQ’s approval is an important step forward to providing patients the only FDA-approved vancomycin oral liquid treatment option for Clostridium difficile associated diarrhea, a life-threatening condition that affects over a half-million patients in the United States annually.”
Upon its launch, which is targeted to be April 2, 2018, FIRVANQ™ will replace CutisPharma’s FIRST®-Vancomycin Unit-of-Use Compounding Kit, which has been available to pharmacists that need a convenient, accurate, and compliant way to compound vancomycin oral liquid therapy. FIRVANQ™ will be commercially available in 25 mg/mL and 50 mg/mL strengths in convenient 150 mL and 300 mL sizes. FIRVANQ™ is designed to be easy to use and has the potential to be a cost-effective alternative to existing vancomycin therapies.
“As a practicing infectious disease physician treating many patients with CDAD, having an FDA-approved vancomycin oral liquid formulation that is affordable and accessible to my patients is very beneficial,” said Stuart Johnson, MD, Loyola University Medical Center. “Patient access is currently limited by the fact that only a select few pharmacies perform compounding in the outpatient setting these days, given the many new regulations in place. Availability of an FDA-approved vancomycin oral liquid treatment will effectively allow any pharmacy to stock this therapy, and hopefully encourage third-party payer reimbursement, significantly improving accessibility and convenience for patients.”
CutisPharma, Inc., based in Wilmington, Mass., is a privately held, specialty pharmaceutical company that has been the industry leader for 20 years in providing innovative solutions to pharmacists. CutisPharma’s FIRST® Unit-of-Use Compounding Kits have benefited millions of patients who are unable to swallow conventional oral dosage forms such as tablets and capsules and whose needs are not served by commercially available therapies. The Company’s first FDA-approved Kit will allow significantly broader patient access, convenience to pharmacists and patients alike by reducing the need for compounding, and serve as a potential cost-saving option to existing treatments. For more information, visit www.cutispharma.com
To provide a background and definition of each of them the following information is beneficial.
Bacteria are a large group of microscopic, unicellular organisms that exist either independently or as parasites. Some bacteria are capable of forming spores around themselves, which allow the organism to survive in hostile environmental conditions. Bacterial spores are made of a tough outer layer of keratin that is resistant to many chemicals, staining and heat. The spore allows the bacterium to remain dormant for years, protecting it from various traumas, including temperature differences, absence of air, water and nutrients. Spore forming bacteria cause a number of diseases, including botulism, anthrax, tetanus and acute food poisoning. (1)
Bacillus is a specific genus of rod-shaped bacteria that are capable of forming spores. They are sporulating, aerobic and ubiquitous in nature. Bacillus is a fairly large group with many members, including Bacillus cereus, Bacillus clausii and Bacillus halodenitrificans. Bacillus spores, also called endospores, are resistant to harsh chemical and physical conditions. This makes the bacteria able to withstand disinfectants, radiation, desiccation and heat. Bacillus are a common cause of food and medical contamination and are often difficult to eliminate.
Clostridium are rod-shaped, Gram-positive (bacteria that retain a violet or dark blue Gram staining due to excessive amounts of peptidoglycan in their cell walls) bacteria that are capable of producing spores. According to the Health Protecton Agency, the Clostridium genus consists of more than a hundred known species, including harmful pathogens such as Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani and Clostridium sordellii.
Some species of the bacteria are used commercially to produce ethanol (Clostridium thermocellum), acetone (Clostridium acetobutylicum), and to convert fatty acids to yeasts and propanediol (Clostridium diolis).
Scientists discovered C. diff in 1935, but they didn’t recognize it as the major cause of antibiotic-associated diarrhea until 1978. The rise of C. diff in the 1970s was triggered by the widespread use of the antibiotic clindamycin. Over the next 20 years, broad-spectrum antibiotics in the penicillin and cephalosporin families fueled the C. diff epidemic, and in the early years of this century, fluoroquinolone antibiotics were linked to a new and more dangerous hypervirulent strain of C. diff.
C. diff is classified as an anaerobic bacterium because it thrives in the absence of oxygen. Like its cousins, the Clostridia that cause tetanus, botulism, and gas gangrene, C. diff passes through a life cycle in which the actively dividing form transforms itself into the spore stage. Spores are inert and metabolically inactive, so they don’t cause disease. At the same time, though, spores are very tough and sturdy; they are hard to kill with disinfectants, and they shrug off even the most powerful antibiotics.
Here’s how C. diff causes trouble. Patients with C. diff shed spores into their feces. Without strict precautions, spores are inadvertently transmitted to hands, utensils, and foods, and then swallowed by someone else. The spores come to life in the second person’s GI tract, but in the best of circumstances, the normal bacteria keep C. diff in check and illness does not develop. But if the “good” GI bacteria have been knocked down by antibiotics, C. diff gets the upper hand. As C. diff multiplies and grows, it produces toxins that injure the lining of the colon, producing diarrhea, inflammation, and sometimes worse. Ordinary strains of C. diff produce two toxins, called toxins A and B, but the new, worrisome hypervirulent strains produce up to 16 times more toxin A and 23 times more toxin B. (2)
C. diff is an old bacterium,…..the CDAD epidemic is new ……..What turned a medical curiosity into a major threat? In a word, antibiotics.
Antibiotics are marvelous medications, and they are obviously here to stay. But doctors must use them wisely. That means prescribing an antibiotic only when it’s truly necessary, choosing the simplest, most narrowly focused drug that will do the job, and stopping treatment as soon as the job is done. Patients can help by resisting the temptation to demand an antibiotic for every potential infection.
When it comes to using antibiotics properly, less can be more.
Sporolactobacillus is a group of anaerobic, rod-shaped, spore forming bacteria that include Sporolactobacillus dextrus, Sporolactobacillus inulinus, Sporolactobacillus laevis, Sporolactobacillus terrae and Sporolactobacillus vineae. Sporolactobacillus are also known as lactic-acid bacteria for they are capable of producing the acid from fructose, sucrose, raffinose, mannose, inulin and sorbitol. Sporolactobacillus are found in the soil and often in chicken feed. According to “Fundamentals of Food Microbiology,” the spores formed by Sporolactobacillus are less resistant to heat than those formed by the Bacillus genus.
Sporosarcina are a group of round-shaped (cocci) aerobic bacteria that include Sporosarcina aquimarina, Sporosarcina globispora, Sporosarcina halophila, Sporosarcina koreensis, Sporosarcina luteola and Sporosarcina ureae. According to “Antibiotic Resistance and Production in Sporosarcina ureae,” Sporosarcina is thought to play a role in the decomposition of urea in the soil.
Revival and Identification of Bacterial Spores in
25- to 40-Million-Year-Old Dominican Amber
Raid J. Cano* and Monica K. Borucki
A bacterial spore was revived, cultured, and identified from the abdominal contents of extinct bees preserved for 25 to 40 million years in buried Dominican amber. Rigorous surface decontamination of the amber and aseptic procedures were used during the recovery of the bacterium. Several lines of evidence indicated that the isolated bacterium was of ancient origin and not an extant contaminant. The characteristic enzymatic, biochemical, and 1 6S ribosomal DNA profiles indicated that the ancient bacterium is most closely related to extant Bacillus sphaericus.
To read the article in its entirety please click on the following link:
“Nexium is one of several proton pump inhibitors (PPI’s) and it’s often prescribed for heartburn to keep the stomach from producing too much acid. Consumer Reports said that ads have helped make Nexium the biggest selling prescription drug today.”
Americans spend $6 billion a year on it, but according to Consumer Reports, Nexium and drugs like it are overused.
“But unless you have gastroesophageal reflux disease — and that’s really when you have heartburn a couple times a week for several months on end — you actually may not need such a strong drug,” said Lisa Gill, Consumer Reports.
To read the article in its’ entirety please click on the link below:
Proton Pump Inhibitors (PPIs) – Drug Safety Communication: Clostridium Difficile-Associated Diarrhea (CDAD) Can be Associated With Stomach Acid Drugs
AcipHex (rabeprazole sodium)
Nexium (esomeprazole magnesium)
Omeprazole (omeprazole) Over-the-Counter (OTC)
Prevacid (lansoprazole) and OTC Prevacid 24hr
Prilosec (omeprazole) and OTC
Protonix (pantoprazole sodium)
Vimovo (esomeprazole magnesium and naproxen)
Zegerid (omeprazole and Sodium bicarbonate) and OTC
AUDIENCE: Gastroenerology, Family Practice, Consumer
ISSUE: FDA notified the public that the use of stomach acid drugs known as proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridium difficile–associated diarrhea (CDAD). A diagnosis of CDAD should be considered for patients taking PPIs who develop diarrhea that does not improve. The FDA is working with manufacturers to include information about the increased risk of CDAD with use of PPIs in the drug labels.
FDA is also reviewing the risk of CDAD in users of histamine H2 receptor blockers. H2 receptor blockers are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and heartburn.
BACKGROUND: Proton pump inhibitors (PPIs) are marketed under various brand and generic drug names as prescription and over-the-counter (OTC) products. They work by reducing the amount of acid in the stomach. Prescription PPIs are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and inflammation of the esophagus. Over-the-counter PPIs are used to treat frequent heartburn.
Clostridium difficile (C. difficile) is a bacterium that can cause diarrhea that does not improve. Symptoms include watery stool, abdominal pain, and fever, and patients may go on to develop more serious intestinal conditions. The disease can also be spread in hospitals.
RECOMMENDATION: Patients should immediately contact their healthcare professional and seek care if they take PPIs and develop diarrhea that does not improve. Information for Healthcare Professionals:
A diagnosis of CDAD should be considered for PPI users with diarrhea that does not improve.
Advise patients to seek immediate care from a healthcare professional if they experience watery stool that does not go away, abdominal pain, and fever while taking PPIs.
Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:
ALLSCHWIL/BASEL, SWITZERLAND – 27 February 2014 – Actelion Ltd (SIX: ATLN) today (27/2/2014) announced that the US Food and Drug Administration (FDA) has designated cadazolid as both a Qualified Infectious Disease Product (QIDP) and a Fast Track development program for the treatment of Clostridium difficile-associated diarrhea (CDAD).
The QIDP designation for cadazolid means that – among other incentives – cadazolid would receive a nine-month priority review upon successful completion of the ongoing global Phase III IMPACT program. The Fast Track designation is intended to promote communication and collaboration between the FDA and the Company on the development of the drug.
The designations are based on the 2012 US Generating Antibiotic Incentives Now (GAIN) Act. The GAIN act is a legislative effort to incentivize the development of new antibiotic agents that target serious life-threatening infections.
Guy Braunstein, M.D. and Head of Clinical Development commented: “Clostridium difficile-associated diarrhea is a very serious and potentially life-threatening infection. There is a great need for an antibiotic that allows effective treatment of CDAD with low recurrence rates, particularly in infections caused by hypervirulent strains. The GAIN act highlights the importance of research in this area and we are very happy to receive the advantages that this designation for cadazolid will afford us.”
ABOUT THE IMPACT PROGRAM
IMPACT is an International Multi-center Program Assessing Cadazolid Treatment in patients suffering from Clostridium difficile-associated diarrhea (CDAD). The program comprises two Phase III studies comparing the efficacy and safety of cadazolid (250 mg administered orally twice daily for 10 days) versus vancomycin (125 mg administered orally four times daily for 10 days).
The IMPACT studies are designed to determine whether the clinical response after administration of cadazolid is non-inferior to vancomycin in subjects with CDAD, and whether administration of cadazolid is superior to vancomycin in the sustained clinical response. The program is expected to enroll approximately 1’280 subjects worldwide, and commenced enrollment in the fourth quarter of 2013.
The novel antibiotic cadazolid is a strong inhibitor of Clostridium difficile protein synthesis leading to strong suppression of toxin and spore formation. In preclinical studies cadazolid showed potent in vitro activity against Clostridium difficile clinical isolates and a low propensity for resistance development. In a human gut model of CDAD, cadazolid had a very limited impact on the normal gut microflora.
Cadazolid absorption is negligible resulting in high gut lumen concentrations and low systemic exposure, even in severe cases of CDAD where the gut wall can be severely damaged and permeability to drugs potentially increased.
ABOUT CADAZOLID IN THE PHASE II STUDY
Cadazolid was studied in a Phase II multi-center, double-blind, randomized, active reference, parallel group, therapeutic exploratory study. The study evaluated the efficacy, safety and tolerability of a 10-day, twice daily oral administration of 3 doses (250 mg, 500 mg or 1,000 mg b.i.d.) of cadazolid in subjects with Clostridium difficile-associated diarrhea (CDAD). As the current standard of care for CDAD, oral vancomycin (125 mg qid for 10 days) was used as the active reference. The study was completed in December of 2012, after having enrolled 84 subjects with CDAD.
The results of the Phase II study indicate that the effect of all doses of cadazolid were numerically similar to, or better than vancomycin on key endpoints including CDAD clinical cure rates as well as sustained cure rates. Clinical cure rate was defined as the resolution of diarrhea and no further need for CDAD therapy at test-of-cure 24 to 72 hours after the last dose of treatment, while sustained cure rate was defined as clinical cure with no recurrence of CDAD up to 4 weeks post-treatment. Recurrence rates were numerically lower for all doses of cadazolid as compared to vancomycin. Cadazolid was safe and well tolerated.
ABOUT THE GAIN ACT (INCLUDING FAST TRACK DESIGNATION)
The Food and Drug Administration Safety and Innovation Act (FDASIA) was signed into law in July 2012. The GAIN Act is Title VIII to FDASIA. The purpose of the GAIN Act is to encourage pharmaceutical research of certain antibiotics by designation of products as QIDPs. These products are intended to treat serious or life-threatening infections and include those to treat certain specifically identified pathogens, which are listed in the GAIN Act. C. difficile is one such specifically identified pathogen and drugs to treat CDAD would be eligible for designation as a QIDP.
The GAIN Act also provides that qualifying drugs (QIDPs) are eligible for inclusion in the FDA’s Fast Track program. This program is intended to facilitate development and expedite review of new drugs and includes close early communication between the FDA and a drug’s sponsor.
ABOUT FAST TRACK DRUG DEVELOPMENT PROGRAMS
For further information regarding Fast Track Drug Development Programs, please refer to the FDA document “Guidance for Industry on Fast Track Drug Development Programs: Designation, Development, and Application Review”. This document is available on the Internet at:
ABOUT CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA
Clostridium difficile is a Gram-positive, anaerobic, spore-forming bacterium that is the leading cause of nosocomial diarrhea. Clostridium difficile-associated diarrhea (CDAD or CDI for Clostridium difficile infection) can be a severe and life-threatening disease and results from the overgrowth in the colon of toxigenic strains of Clostridium difficile, generally during or after therapy with broad-spectrum antibiotics. CDAD is a major healthcare problem and a leading cause of morbidity in elderly hospitalized patients. The frequency and severity of CDAD in the western world has increased in recent years, and new hypervirulent and epidemic strains of Clostridium difficile have been discovered that are characterized by overproduction of toxins and other virulence factors, and by acquired resistance to fluoroquinolones such as moxifloxacin.
Current antibiotic therapy for CDAD includesvancomycin and metronidazole. While clinical cure rates are generally 85-90%, recurrences rates of 15-30 % with either drug are problematic as Clostridium difficile produces spores that are resistant to antibiotic treatment and routine disinfection. Spores surviving in the gut of patients and/or in the hospital environment may play a major role in re-infection and recurrence of CDAD after antibiotic treatment. Vancomycin and metronidazole are reported to promote spore formation in vitro at sub-inhibitory concentrations.
Only one new antibiotic, fidaxomicin, has been approved over the last 30 years for this indication, and there remains a need for new drugs with improved properties, in particular, antibiotics that allow effective treatment of infections caused by hypervirulent strains, with low recurrence rates.
1. Baldoni D, et al. J. Antimicrob. Chemother. Published online ahead of print.
2. Louie TJ, et al. Abstract/poster LB-2956, 53rd European Congress of Clinical Microbiology and Infectious Diseases.
3. Gerding DN, et al. Abstract/poster K-168, 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy.
4. Mackie AE, et al. Abstract/poster A-008, 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy.
5. Chilton CH, et al. J. Antimicrob. Chemother. Published online ahead of print.
6. Locher HH, et al. Antimicrob. Agents Chemother. 58:901-908.
7. Locher HH, et al. Antimicrob. Agents Chemother. 58: 892-900.
8. Rashid MU, et al. Anaerobe 20: 32-35.
9. Hecht DW, et al. Abstract/poster E-808 of the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy.
Actelion Ltd. is a leading biopharmaceutical company focused on the discovery, development and commercialization of innovative drugs for diseases with significant unmet medical needs.
Actelion is a leader in the field of pulmonary arterial hypertension (PAH). Our portfolio of PAH treatments covers the spectrum of disease, from WHO Functional Class (FC) II through to FC IV, with oral, inhaled and intravenous medications. Although not available in all countries, Actelion has treatments approved by health authorities for a number of specialist diseases including Type 1 Gaucher disease, Niemann-Pick type C disease, Digital Ulcers in patients suffering from systemic sclerosis, and mycosis fungoides in patients with cutaneous T-cell lymphoma.
Founded in late 1997, with now over 2,400 dedicated professionals covering all key markets around the world including the US, Japan, China, Russia and Mexico, Actelion has its corporate headquarters in Allschwil / Basel, Switzerland. Actelion shares are traded on the SIX Swiss Exchange (ticker symbol: ATLN) as part of the Swiss blue-chip index SMI (Swiss Market Index SMI(R)). All trademarks are legally protected.
The above information contains certain “forward-looking statements”, relating to the company’s business, which can be identified by the use of forward-looking terminology such as “estimates”, “believes”, “expects”, “may”, “are expected to”, “will”, “will continue”, “should”, “would be”, “seeks”, “pending” or “anticipates” or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company’s investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company’s existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected.
Actelion Pharmaceuticals Ltd : Actelion’s novel antibiotic cadazolid receives US FDA Qualified Infectious Disease Product designation for the treatment of Clostridium difficile-associated diarrhea . Processed and transmitted by Nasdaq OMX Corporate Solutions. The issuer is solely responsible for the content of this announcement.
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Source: Actelion Pharmaceuticals Ltd via Globenewswire