Tag Archives: Recurrent CDI

U.S. Food and Drug Administration (FDA) Has Approved Merck’s (MSD) ZINPLAVA ™ (bezlotoxumab) Injection 25mg/ml To Reduce Recurrence Of Clostridium difficile Infection In Patients 18 Years Of Age Or Older

MERCKBW2015_medLogoBLK [Converted] (2)

Merck  known as MSD outside the United States and Canada, on October 22, 2016 announced that the U.S. Food and Drug Administration (FDA) has approved ZINPLAVA™ (bezlotoxumab) Injection 25 mg/mL.

Merck anticipates making ZINPLAVA available in first quarter 2017.

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 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.

Please see Prescribing Information for ZINPLAVA (bezlotoxumab) at http://www.merck.com/product/usa/pi_circulars/z/zinplava/zinplava_pi.pdf 

 

Patient Information for ZINPLAVA at http://www.merck.com/product/usa/pi_circulars/z/zinplava/zinplava_ppi.pdf

CDI is caused by bacteria that produce toxins, including toxin B. Symptoms of CDI include mild-to-severe diarrhea, abdominal pain and fever. The incidence of recurrent CDI is higher in certain patient populations, including people 65 years of age or older and those with compromised immune systems.

“For generations, Merck has been steadfast in its commitment to fighting infectious diseases – and that commitment continues today. ZINPLAVA is a human monoclonal antibody that binds to C. difficile toxin B and neutralizes its effects,” said Dr. Nicholas Kartsonis, vice president of clinical development, infectious diseases, Merck Research Laboratories.

Selected safety information about ZINPLAVA

Heart failure was reported more commonly in the two Phase 3 clinical trials in ZINPLAVA-treated patients compared to placebo-treated patients. These adverse reactions occurred primarily in patients with underlying congestive heart failure (CHF). In patients with a history of CHF, 12.7% (15/118) of ZINPLAVA-treated patients and 4.8% (5/104) of placebo-treated patients had the serious adverse reaction of heart failure during the 12-week study period. Additionally, in patients with a history of CHF, there were more deaths in ZINPLAVA-treated patients [19.5% (23/118)] than in placebo-treated patients [12.5% (13/104)] during the 12-week study period. The causes of death varied, and included cardiac failure, infections, and respiratory failure. In patients with a history of CHF, ZINPLAVA (bezlotoxumab) should be reserved for use when the benefit outweighs the risk.

The most common adverse reactions occurring within 4 weeks of infusion with a frequency greater than placebo and reported in ≥4% of patients treated with ZINPLAVA and Standard of Care (SoC) antibacterial drug therapy vs placebo and SoC antibacterial drug therapy included nausea (7% vs 5%), pyrexia (5% vs 3%) and headache (4% vs 3%).

Serious adverse reactions occurring within 12 weeks following infusion were reported in 29% of ZINPLAVA-treated patients and 33% of placebo-treated patients. Heart failure was reported as a serious adverse reaction in 2.3% of ZINPLAVA-treated patients and 1.0% of placebo-treated patients.

In ZINPLAVA-treated patients, 10% experienced one or more infusion specific adverse reactions compared to 8% of placebo-treated patients, on the day of or the day after, the infusion. Infusion specific adverse reactions reported in ≥0.5% of patients receiving ZINPLAVA and at a frequency greater than placebo were nausea (3%), fatigue (1%), pyrexia (1%), dizziness (1%), headache (2%), dyspnea (1%) and hypertension (1%). Of these patients, 78% experienced mild adverse reactions, and 20% of patients experienced moderate adverse reactions. These reactions resolved within 24 hours following onset.

As with all therapeutic proteins, there is a potential for immunogenicity following administration of ZINPLAVA. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to bezlotoxumab in two Phase 3 studies with the incidence of antibodies in other studies or to other products may be misleading. Following treatment with ZINPLAVA in these two studies, none of the 710 evaluable patients tested positive for treatment-emergent anti-bezlotoxumab antibodies.

About bezlotoxumab

Bezlotoxumab was developed by researchers at the University of Massachusetts Medical School’s MassBiologics Laboratory in conjunction with Medarex (now part of Bristol-Myers Squibb), and was licensed to Merck in 2009.

Please see Prescribing Information for ZINPLAVA (bezlotoxumab) at http://www.merck.com/product/usa/pi_circulars/z/zinplava/zinplava_pi.pdf 

 

About Merck

For 125 years, Merck has been a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships.

For more information, visit www.merck.com

To read this article in its entirety please click on the following link

http://www.pharmiweb.com/PressReleases/pressrel.asp?ROW_ID=187373#.WAsjR8li9kk

 

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

Microbiome – C. diff. Treatments On The Horizon

NewsUpdate

 

 

 

PROBIOTICS:

Pick a disease or disorder, and somebody, somewhere, has said that a probiotic supplement—an over-the-counter, unregulated pill usually filled with a single strain of friendly gut bacteria—might cure it, whether it’s cancer, obsessive-compulsive disorder, or a yeast infection.

But there’s very little evidence that probiotic supplements do any good. “There’s a lot of promise here but not a lot of proof yet,” said Cliff McDonald, associate director for science at the Centers for Disease Control and Prevention’s Division of Healthcare Quality Promotion.

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CDC Reports:

Half a million people a year are infected with C. diff in the U.S., the CDC estimates, with 29,000 annual deaths related to the diarrheic bacterium. More than 65 percent of C. diff infections involve exposure in a health-care facility, according to a 2015 study, creating more than $4.8 billion in excess health-care costs at acute-care facilities alone.

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C. diff. Treatments On The Horizon:

To Learn More About ALL C. diff. Clinical Trials In Progress Click On The Following Link:

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

 

Seres Therapeutics, a microbiome-based biopharmaceutical company in Cambridge, Mass., is developing a pill, subject to a rigorous approval process under the Food and Drug Administration, to tackle recurrent Clostridium difficile. (The digestive system’s microbiome is the community of healthy gut bacteria that normally reside in the body.)

Seres aims to put the science behind a proven treatment of recurrent C. diff, fecal transplants, in a pill, which wouldn’t require a colonoscopy. Like probiotic supplements, it’s a gut bacteria product. Unlike the supplements, by the time it’s available it will have gone through the FDA wringer. It will contain about 50 strains of bacteria proven effective in treating C. diff and will require a doctor’s prescription.

Recurrent C. diff is an obvious entry point for Seres, said Chief Executive Officer Roger Pomerantz. “We asked, what is the lowest-hanging fruit?” But it’s hardly the end. The company has built a microbiome library of 14,000 strains of human bacteria it hopes will help it treat a range of diseases, eventually without needing feces at all.   Seres has embarked on the research with some pretty lofty goals, including finding treatments for obesity, liver disease, and cancer. It has partnerships with Massachusetts General Hospital, the Mayo Clinic, Memorial Sloan Kettering Cancer Center, and other respected medical institutions.  “We will figure out exactly what’s wrong with the microbiome, design a drug, and then pull the organisms out with our library, never touching a human donation,” Pomerantz said.    Seres’s lead product candidate, SER-109, will treat recurrent C. diff with four capsules taken orally instead of with transplants. While fecal matter is the raw material for the pills, the final product consists only of the spores necessary to treat the infection, which will have been extracted and purified.  SER-109 is expected to become the first oral microbiome therapy approved by the FDA, though Seres declined to predict exactly when it will arrive. Results from the latest trials are due by midyear, and Phase 3 trials are scheduled to follow later in the year. Seres hopes to follow up quickly with SER-287, a drug to treat ulcerative colitis, which could be the first microbiome drug to treat a chronic disease, and SER-262, to treat primary C. diff before it turns into the recurrent kind.

Other companies are racing to collect enough data for FDA approval, but right now Seres, which is publicly traded, looks to be the one to beat. “Seres is probably going to be the first one that’s going to knock at the FDA’s door,” said Mohan Iyer, chief business officer at Second Genome, a microbiome company studying how to treat disease with the compounds produced by gut bacteria instead of the gut bacteria themselves.

“SER-109 is poised to be first-in-class among fecal microbiota transplant-derived drugs,” Joseph Schwartz, an analyst at Leerink Partners, wrote in a May report. The report says the latest trial results “wowed the Street” but warns that the company could still be held back by “disappointing clinical data” and obstacles in the regulatory process.

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Another top contender is Rebiotix. Its RBX2660 is also designed to treat recurrent C. diff but, unlike SER-109, is administered with an enema; an oral version is in development. The treatment also differs significantly from Seres’s in formulation, including thousands of kinds of microbes from the donor’s stool, compared with SER-109’s 50 or so, as many as could be preserved and some of which haven’t even been identified.

“We make sure we have a minimum concentration of certain kinds that we know the patients lack,” CEO Lee Jones said. “But we don’t identify all of them. There’s no way to do that.” A recent study estimated that 1014 bacteria are in the human gut, most of which have never been isolated. Jones said the drug could hit the market by 2018.

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  • UPDATES:

The medications have been shown to be similarly effective—with no C. diff-associated diarrhea for 29 of 30 of Seres’s patients  and  27 of 31 of Rebiotix’s, in the companies’ latest results—and equally safe. Adverse reactions for both are limited to such problems as moderate diarrhea and abdominal cramping, which could be from the C. diff itself. Both have been designated as “breakthrough therapies” by the FDA, allowing for an expedited approval process, and both are likely soon to provide an at-home alternative to fecal transplants.

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Point Of View:

“I don’t know who is going to make it across the line first,” said Gail Hecht, director of gastroenterology and nutrition at Loyola University Medical Center and chairwoman of the American Gastroenterological Association for Gut Microbiome Research & Education. Hecht has attended a Seres advisory board meeting but doesn’t have a financial interest in the company. “It is indeed a race,” she said.

Seres does have at least one distinct market advantage. “Patients have different preferences,” Hecht observes, but “in general, people don’t particularly like enemas.”

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Human Fecal Transplants:

For nearly two thousand years, doctors have looked to this unlikeliest of places for medicine. One of the earliest documented applications is from the fourth-century Chinese medical doctor Ge Hong, whose “yellow soup” recipe to treat diarrhea included a healthy person’s dried or fermented feces. Sixteen hundred years later, in 1958, patients infected with C. diff received the first known human fecal transplants.

Stool Bank Information: 

Today the effectiveness of fecal transplants (formally known as fecal microbiota transplants) to treat recurrent C. diff is supported by a long list of studies, with researchers attributing the results to the restoration of the microbiome. OpenBiome, a nonprofit stool bank, shipped 1,828 treatments in 2014, a number that ballooned to 7,140 treatments in 2015 and looks to be eclipsed this year, with 4,323 treatments shipped to its clinical partners through May 31. And these numbers don’t take into account the transplants performed through directed fecal donations.

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To read article in its entirety:

http://www.bloomberg.com/news/articles/2016-06-30/coming-soon-gut-bacteria-that-actually-cure-your-disease

Summit Therapeutics To Present Further Data Showing Superiority Of Its New Antibiotic At the 26th ECCMID Conference

summit

 

 

Summit Therapeutics is to present further data showing the superiority of its new antibiotic for hospital superbug C.diff. over the standard of care medicine.

The additional data on Summit’s ridinilazole versus vancomycin comes from the from the Phase 2 CoDIFy trial and will be heard at the 26th European Congress of Clinical Microbiology and Infectious Diseases Conference  (ECCMID).

(ECCMID 2016  Will be hosted in Amsterdam from 9 – 12 April )

Taking the antibiotic ridinilazole resulted in a marked reduction in rates of C. diff. (CDI) recurrence as compared to vancomycin (14.3% versus 34.8%) the drug discovery firm will say.

This result comes on top of t previously reported statistical superiority in ‘sustained clinical response’ rates of ridinilazole over vancomycin (66.7% compared to 42.4%) for treating the disease.

Sustained clinical response is defined as clinical cure at the end of treatment and no recurrence of the condition in 30 days after therapy.

C. diff is a serious threat in hospitals and care homes and there are between 450000 and 700000 cases in the US annually.

Recurrence is a key problem as repeat episodes are typically more severe and associated with an increase in mortality rates and healthcare costs.

 

 

To read the total article, click on the following link:

http://www.menafn.com/1094678222/Summit-Therapeutics-to-present-further-data-showing-ridinilazoles-superiority

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

 

 

 

Comparison Study Shows Efficacy in Frozen Fecal Product To Fresh For Fecal Microbiota Transplantation To Treat Recurrent C. diff. Infections

Frozen fecal microbiota transplantation showed efficacy comparable to fresh FMT for clinical resolution of diarrhea among adult patients with recurrent or refractory Clostridium difficile infection, according to results of a randomized trial published in JAMA.

Using frozen FMT would reduce costs associated with donor screening frequency, provide immediate availability of the treatment and enable delivery of the treatment to centers without on-site laboratory facilities,

the researchers wrote. “Previous studies have supported the use of frozen FMT for management of recurrent [C. difficile infection] but have not directly compared frozen with fresh FMT.”

Lee CH, et al. JAMA. 2016;doi:10.1001/jama.2015.18098

Malani PN, Rao K. JAMA. 2016;doi:10.1001/jama.2015.18100

Christine H. Lee, MD, from McMaster University in Canada, and colleagues, conducted a double-blind, noninferiority trial involving 232 adult patients with recurrent or refractory C. difficile infection (CDI) at six Canadian academic medical centers from July 2012 to September 2014. Patients were randomly assigned to receive frozen (n = 114) or fresh (n = 118) FMT via enema without bowel preparation, and if they showed no improvement by day 4, they received an additional FMT between days 5 and 8.

No recurrence of CDI-related diarrhea at 13 weeks and adverse events served as primary outcomes, and a 15% margin was set to confirm noninferiority.

In the per-protocol population (frozen, n = 91; fresh, n = 87), 83.5% of the frozen FMT group achieved clinical resolution compared with 85.1% of the fresh FMT group, a difference of – 1.6% (95% CI, – 10.5% to ∞; P = .01 for noninferiority). In the modified intention-to-treat population (frozen, n = 108; fresh, n = 111), 75% of the frozen FMT group achieved clinical resolution compared with 70.3% of the fresh FMT group, a difference of 4.7% (95% CI, – 5.2% to ∞; P < .001 for noninferiority). Adverse and serious adverse events were comparable between groups; the most common adverse events were transient diarrhea (70%), abdominal cramps (10%) or nausea (< 5%) during the 24 hours after FMT, and constipation (20%) and excess flatulence (25%) during follow-up, all mild to moderate in severity.

“Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea,” the researchers concluded. “Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting.”

These researchers have provided

“the best evidence to date supporting the use of frozen stool, with their finding that use of frozen stool for FMT resulted in a rate of clinical resolution of diarrhea that was no worse than that obtained with fresh stool for FMT and will likely expand the availability of FMT for patients with recurrent CDI,”

Preeti N. Malani, MD, MSJ, associate editor of JAMA, and Krishna Rao, MD, MS, both from the University of Michigan Health System, Ann Arbor, wrote in a related editorial. “The ability to use frozen stool eliminates many of the logistical burdens inherent to FMT, because stool collection and processing need not be tied to the procedure date and time.

This study also provides greater support for the practice of using centralized stool banks, which could further remove barriers to FMT by making available to clinicians safe, screened stool that can be shipped and stored frozen and thawed for use as needed. In theory, procedure costs may also be decreased, since comprehensive donor screening is expensive.” – by Adam Leitenberger

Disclosures: Lee reports she has participated in clinical trials for ViroPharma, Actelion, Cubist and Merck, and served as a member of the advisory boards for Rebiotix and Merck. Please see the study for a full list of all other researchers’ relevant financial disclosures. Malani and Rao report no relevant financial disclosures.dR

TO READ ARTICLE IN ITS ENTIRETY CLICK ON LINK BELOW:

http://www.healio.com/gastroenterology/infection/news/online/%7Bbac5a422-a30c-4501-8e35-05e9a346772a%7D/frozen-fmt-noninferior-to-fresh-fmt-for-treating-recurrent-c-difficile-infection