Tag Archives: FDA

US Food and Drug Administration (FDA) Issued a Safety Alert About Potential Risks of Serious, Even Life-Threatening Infections Linked To Fecal Microbiota Transplantation (FMT)

The US Food and Drug Administration (FDA) yesterday issued a safety alert about the potential risk of serious, even life-threatening, infections linked to fecal microbiota transplantation (FMT) after six patients were infected with diarrhea-causing Escherichia coli following the procedure.  March 13, 2020

According to the alert, two patients developed enteropathogenic E coli (EPEC) infections, and four developed Shiga toxin–producing E coli (STEC), after receiving FMT for Clostridoides difficile infection. Four of the six patients required hospitalization.

“FDA is informing patients and healthcare providers of the potential risk of transmission of pathogenic bacteria by FMT products and the resultant serious adverse reactions that may occur,” the agency said. “Patients considering FMT for the treatment of C. difficile infection should speak to their health care provider to understand the associated risks.”

STEC is a pathogenic form of E coli that causes abdominal pain, bloody diarrhea, vomiting, and mild fever. EPEC generally doesn’t cause any symptoms, but some strains can cause diarrhea.

Change in screening protocols

The stool used in the procedures all came from Boston-based OpenBiome, the country’s largest stool bank. The company said in a press release yesterday that the cases are the first reports of likely transmission of pathogens by FMT involving stool that came from OpenBiome, which has shipped more than 50,000 FMT treatments to physicians since 2013.

The patients who developed the infections received FMT product prepared from three OpenBiome donors. The two patients who developed EPEC infections were treated with stool from two donors, and the six STEC patients received stool from one donor. OpenBiome says all unused material from the donors has been destroyed.

The FDA says bacterial isolates from the patients’ stools are not yet available to determine if the STEC or EPEC organisms are genetically identical to the organisms from the stool donors—a finding that would confirm that the donor stool was the source of the infection.

In response to the safety alert, OpenBiome says it is immediately implementing changes to its screening program in collaboration with the FDA.

While the company has previously screened donor samples for STEC via enzyme immunoassay, and says the donor involved in the STEC cases tested negative at all screens, OpenBiome will add polymerase chain reaction (PCR) testing for STEC to its screening process. PCR tests on retained donor samples conducted after Openbiome was notified of the infections were found to be positive for STEC.

The retained stool samples from the donors linked to the EPEC infections were found to be positive for EPEC upon further testing from OpenBiome. The company says it has not previously screened donors for EPEC, a position based on international and national guidelines, but will immediately implement EPEC screening by PCR into its donor screening protocol.

“In addition to updating and implementing STEC and EPEC screening into our quality and safety protocols, OpenBiome is also working with FDA to implement retrospective screening of units to ensure that available material meets these new standards,” the company said.

After reporting the infections to the FDA, OpenBiome received information that two additional FMT recipients who received stool from the donor linked to the STEC infections had died. The company said in an update today that the treating clinician for one of the patients determined that the patient had died from underlying cardiac causes, and testing for STEC was not performed. In the second case, testing of donor material was negative for STEC.

“Therefore, it was determined that the death was unrelated to STEC,” the company said.

FMT safety issues

FMT has been found in several studies to be a highly effective treatment for recurrent C difficile infections that aren’t responding to antibiotics, and at least 10,000 FMT procedures for recurrent C difficile are performed each year. FMT is also being investigated for treating other conditions in more than 300 trials.

The idea behind the procedure is to introduce healthy bacteria from a donor into the gut microbiome of a sick recipient and restore the balance between good and bad bacteria.

But this is the second safety alert issued by the FDA regarding FMT. In June 2019, the agency warned of the potential for dangerous infections after two FMT patients developed drug-resistant bloodstream infections and one died, and the agency halted a number of FMT trials until additional screening measures could be put in place. A subsequent paper in the New England Journal of Medicine revealed that the two patients, both of whom were enrolled in clinical trials at Massachusetts General Hospital in Boston, had extended-spectrum beta-lacatamase (ESBL)-producing E coli in their blood.

The two patients had both received stool from Mass General that came from the same donor. While the hospital had screened the stool for C difficile and the presence of drug-resistant pathogens by the hospital, it had not screened it for ESBL-producing E coli. The authors of the paper could not conclusively attribute the infections to FMT, but suspected the patients likely acquired the pathogen from the procedure.

RESOURCE:  http://www.cidrap.umn.edu/news-perspective/2020/03/fda-warns-about-infections-linked-fecal-microbiota-transplants?utm_source=dlvr.it&utm_medium

 

 

U.S. Food and Drug Administration (FDA) Has Accepted 2 New Drug Applications (NDA) for DIFICID (fidaxomicin) In Children Aged Six Months Or Older

OCTOBER 2019

Merck

Known as MSD outside the United States and Canada

announced the U.S. Food and Drug Administration (FDA) has accepted for review a New Drug Application (NDA) for DIFICID ® (fidaxomicin) for oral suspension, and a supplemental NDA (sNDA) for a new indication for use of DIFICID tablets and oral suspension for the treatment of Clostridium (also known as Clostridioides ) difficile infections (CDI) in children aged six months or older. Both applications have received a priority review classification by the FDA. The Prescription Drug User Fee Act (PDUFA), or target action date for both applications, is set for Jan. 24, 2020. The investigational pediatric indication for DIFICID was granted Orphan Drug Designation (ODD) in 2010.

“Evidence indicates the increasing incidence of C. difficile -associated diarrhea among hospitalized children 1,” said Dr. Nicholas Kartsonis, senior vice president, Clinical Research, infectious diseases and vaccines, Merck Research Laboratories. “The filings for the pediatric indication for the new investigational oral suspension formulation of DIFICID, as well as for DIFICID tablets, underscore Merck’s focus and dedication to developing infectious disease treatments for those with unmet needs.”

The sNDA is based primarily on results of the Phase 3 SUNSHINE study 2, which were presented as part of the Late Breaker Oral Abstracts on Emerging Infections at IDWeek 2018 in San Francisco, California.

About DIFICID (fidaxomicin)

DIFICID is a macrolide antibacterial medicine indicated in adults (18 years of age or older) for treatment of Clostridium difficile -associated diarrhea (CDAD). To reduce the development of drug-resistant bacteria and maintain the effectiveness of DIFICID and other antibacterial drugs, DIFICID should be used only to treat infections that are proven or strongly suspected to be caused by Clostridiumdifficile. DIFICID is contraindicated in patients who have known hypersensitivity to fidaxomicin or any other ingredient in DIFICID. DIFICID should only be used for the treatment of C. difficile-associated diarrhea. DIFICID is not effective for the treatment of other types of infections due to minimal systemic absorption of fidaxomicin.

To review the article in its entirety click on the following link to be redirected.  Thank you.

http://www.oleantimesherald.com/business/fda-accepts-two-applications-for-merck-s-dificid-fidaxomicin-to/article_c1787f52-e9e0-5dd3-bb8c-adb22019d8b3.html

U.S. Food and Drug Administration (FDA) Grants Fast Track Status to Acurx Pharmaceuticals for New Investigational Antibiotic for Clostridium difficile Infection

FDA grants Fast Track status to new C difficile antibiotic

The US Food and Drug Administration (FDA) has granted Fast Track designation to a new investigational antibiotic for Clostridioides difficile infection (CDI), according to a press release yesterday from Acurx Pharmaceuticals.

ACX-362E is a novel, narrow-spectrum oral antibiotic based on inhibition of the enzyme DNA polymerase IIIC, which is required for bacterial replication and pathogenesis in C difficile.

The drug is currently being tested in a phase 1 clinical trial. The company expects to launch a phase 2 trial at the end of year.

Under the Fast Track designation, ACX-362E will receive expedited review from the FDA. The agency grants the designation to drugs that treat serious or life-threatening conditions and fulfill an unmet medical need. The CDC has identified C difficile, which sickens nearly 500,000 Americans each year, as an urgent threat.

“If approved, we believe our new antibacterial, ACX-362E, will be an important therapeutic alternative for patients with CDI,” Acurx managing partner Robert DeLuccia said in the press release. “The Fast Track designation will allow Acurx to work more closely with the FDA to bring ACX-362E to physicians and patients as soon as possible.”
Jan 16 Acurx Pharmaceuticals press release

Information Explaining the “Right to Try” Legislation and What It Means To Terminally Ill Patients

Q: What is the Right to Try Act?

A: Right To Try is legislation that allows terminally ill patients to access investigational treatments that have passed basic safety testing (Phase I) with the FDA, but are not yet available on pharmacy shelves.

Q: Why was Right To Try developed?

A: Over 1 million Americans die from a terminal illness every year. Many spend years searching for a potential cure, or struggle in vain to get accepted into a clinical trial. Unfortunately, FDA red tape and government regulations restrict access to promising new treatments, and for those who do get access, it’s often too late.

Q: Is Right To Try law in my state?

A: Right To Try has been signed into law in 38 states and counting: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Michigan, Minnesota, Mississippi, Missouri, Montana, Nevada, New Hampshire, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, South Carolina, South Dakota, Tennessee, Texas, Utah, Virginia, West Virginia, Washington, and Wyoming. If your state is not listed, and you want to bring Right to Try to your state, click here to find out how.

For more information about the “right-to-try” legislation please click on the following link to be redirected:

http://righttotry.org/faq/

The Senate in August 2017 passed by unanimous consent a measure designed to make it easier for terminally ill patients to get access to experimental treatments without oversight from the U.S. Food and Drug Administration (FDA)

The “right-to-try” legislation has been championed by the libertarian Goldwater Institute, which has worked to pass similar legislation in 37+ states.

The federal version, now headed to the House, would bar the government from blocking patients from getting access to medications that have undergone only preliminary testing in humans. Patients first would have to try all other available treatments and be ineligible for clinical trials.

The bill would provide drug companies some legal protection if a treatment results in harm.

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

https://www.denverpost.com/2017/08/03/right-to-try-terminally-ill-patients-experimental-drugs-fda/

 

 

 

 

Learn More About Clostridium difficile (C.diff., C.difficile) infection and Recurrent CDI Clinical Trials In Progress

 

 

 

The C Diff Foundation has implemented a global campaign to raise awareness of Clostridium difficile infection (C.difficile) clinical trials, clinical studies, clinical research and observational studies evaluating interventions for C. difficile prevention, treatments, and environmental safety.

In the USA: Nearly half a million Americans suffer from Clostridium difficile (C. diff.) infections in a single year according to a study released in 2015 by the Centers for Disease Control and Prevention (CDC). Approximately 29,000 patients died within 30 days of the initial diagnosis of C. difficile. Of those, about 15,000 deaths were estimated to be directly attributable to C. difficile infections making C. difficile a very important cause of infectious disease death in the United States.

“Clostridium difficile infections are not only the most common cause of healthcare-acquired infections in the United States but also very common in the community in younger patients who previously were thought to be less susceptible to C. difficile. The rate of recurrent C. difficile infections is increasing tremendously and this increase is higher than the rate of primary C. difficile infections,” stated Sahil Khanna, MD, Assistant Professor of Medicine Division of Gastroenterology and Hepatology, Director of the C. difficile Clinic, Fecal Microbiota Transplantation program and C. difficile related Clinical Trials, Mayo Clinic, Rochester, MN.

Dr. Khanna also added, “It is imperative and important for clinical trials to be done to advance the development of new treatments, new medications, and new ways to prevent and treat Clostridium difficile infections.”

Individuals volunteer to participate in clinical trials in hopes of improving their own health, to access treatments that might not be available otherwise, often because they are new and not yet widely available. They help others by contributing to advances in medicine. There can also be potential risks participating in clinical trials and clinical studies. All of the known risks associated with a particular trial and or study will be discussed during the informed consent process. It will be thoroughly explained in the informed consent document that a volunteer will receive from the research staff prior to participating in any study.

To learn more about clinical research (e.g., Clostridium difficile, C.difficile) visit the U.S. Food and Drug Administration http://www.fda.gov or telephone 1-800-835-4709, The National Institutes of Health (NIH) http://www.nih.gov and ClinicalTrials.gov.

“Clinical trials are vital to improving our knowledge about how best to prevent and treat C. difficile infections. Informing patients of clinical trials is important, and in recent years several clinical trials have led to significant improvements in the treatments available for patients with C. difficile infections,” stated Mark Wilcox, MD, FRCPath, Consultant Microbiologist, Head of Microbiology and Academic Lead of Pathology Leeds Teaching Hospitals, Professor of Medical Microbiology University of Leeds Institute of Biomedical and Clinical Sciences, Lead on Clostridium difficile for Public Health England, UK.

About the U.S. Food and Drug Administration (FDA):
The FDA is responsible for protecting the public health by assuring that foods are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drug, and vaccines and other biological products and medical devices intended for human use are safe and effective. FDA’s responsibilities extend to the 50 United States, the District of Columbia, Puerto Rico, Guam, the Virgin Islands, American Samoa, and other U.S. territories and possessions.

About the National Institutes of Health (NIH):
The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency making important discoveries that improve health and save lives.

About ClinicalTrials.gov
ClinicalTrials.gov is a Web-based resource that provides patients, their family members, health care professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions.