Tag Archives: Merck

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/.

 

 

MODIFY Trials Showed That Taking bezlotoxumab (Merck), a Monoclonal Antibody That Neutralizes Clostridium difficile Toxin B, Led To Lower Recurrence of C. difficile Infection and Fewer Hospital Re-admissions

In The News

A post hoc and subpopulation analysis of the MODIFY trials showed that taking bezlotoxumab (MERCK) , a monoclonal antibody that neutralizes Clostridium difficile toxin B, led to lower recurrence of C. difficile infection and fewer hospital readmissions among European patients compared with placebo, according to study data presented at ECCMID 2016.

MODIFY I and II were global phase 3 trials that demonstrated the safety and efficacy of a single 10 mg/kg IV dose of bezlotoxumab (Merck) to decrease C. difficile recurrence when paired with standard antibiotic therapy. While initial antibiotic treatment for C. difficile is often successful, up to 35% of patients experience a recurrence of the infection, with each recurrence increasing the risk for future recurrences.

In the post hoc analysis, researchers studied a subset of European patients from the MODIFY trials who received standard antibiotic treatment plus either bezlotoxumab (n = 313) or placebo (n = 293).

Analysis showed that the recurrence of C. difficile in the bezlotoxumab group was 15% vs. 24.2% in the placebo group (difference, –9.2%; 95% CI, –15.6 to –2.9). These rates were consistent with those observed in the overall group of patients in the MODIFY trials, according to the researchers. Further, just 4.5% of European patients in the bezlotoxumab group experienced hospital readmission associated with C. difficile infection compared with 13.3% in the placebo group (difference, –8.8%; 95% CI, –13.9 to –4). All-cause hospital readmissions were 23% in the bezlotoxumab group and 26.6% in the placebo group (difference, –3.5%; 95% CI –11 to 3.9).

Results of two other post hoc analyses of the MODIFY trials also were presented at ECCMID 2016.

In one, researchers showed that giving bezlotoxumab to patients receiving standard antibiotic care was effective through 12 weeks in key subpopulations at high risk for C. difficile recurrence and/or C. difficile infection-related adverse outcomes, including those aged 65 years and older, those with at least one C. difficile infection within the previous 6 months, and those who were immunocompromised.

Another post hoc analysis showed that the magnitude of reduction in rates of C. difficile recurrence in patients taking bezlotoxumab compared with placebo was greater when diagnosis was made using enzyme immunoassays for toxin detection (–12.8%; 95% CI –18.5 to –7) rather than PCR (–6.5%; 95% CI –12.8 to –0.3). The results were clinically meaningful no matter the testing method, the researchers said. – by Gerard Gallagher

To read full article click on the following link:

http://www.healio.com/infectious-disease/gastrointestinal-infections/news/online/%7B2c78b819-6147-45a8-b615-aee90fc4d5ce%7D/bezlotoxumab-helps-to-reduce-cdi-recurrence-hospital-readmissions

 

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

Merck Shares Significant Details Associated With Their Ongoing Dedication Fighting Infectious Diseases Through More Than 30 Scientific Presentations At ECCMID

In The News:

Researchers are scheduled to provide more than 30 scientific data presentations on the company’s established and investigational infectious disease medicines and vaccines at this year’s 26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)

∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞∞

Merck, known as MSD outside the United States and Canada,  announced that researchers are scheduled to provide more than 30 scientific data presentations on the company’s established and investigational infectious disease medicines and vaccines at this year’s 26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)
April 9-12 , 2016 in Amsterdam, Netherlands.

Presentations at ECCMID will include new data analyses from two pivotal Phase 3 clinical trials of bezlotoxumab, Merck’s investigational compound for the prevention of Clostridium difficile (C. difficile) infection recurrence in patients on standard-of-care antibiotics for the treatment of C. difficile infection. Researchers also will present studies showing updated data on the in vitro activity of ZERBAXA® (ceftolozane and tazobactam) 1.5 g. ZERBAXA is indicated for the treatment of adults with complicated urinary tract infections (cUTI), including pyelonephritis, and in combination with metronidazole, complicated intra-abdominal infections (cIAI) caused by designated susceptible Gram-negative and Gram-positive bacteria. For more information, including a complete list of abstract titles, please visit the ECCMID website at www.eccmid.org.

Merck’s commitment to infectious diseases

For more than 80 years, Merck has contributed to the discovery and development of novel medicines and vaccines to combat infectious diseases. In addition to a combined portfolio of antibiotic and antifungal medicines, vaccines, and medicines for HIV and HCV, Merck has multiple programs that span discovery through late-stage development. Merck currently has 10 compounds in Phase 2/Phase 3 clinical trials for the potential treatment or prevention of infectious diseases.

About ZERBAXA

ZERBAXA (ceftolozane and tazobactam) is an antibacterial combination product for intravenous infusion consisting of the cephalosporin antibacterial drug ceftolozane sulfate and the beta-lactamase inhibitor tazobactam sodium.

ZERBAXA is approved in the United States and is indicated in adult patients for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. ZERBAXA used in combination with metronidazole is indicated in adult patients for the treatment of complicated intra-abdominal infections (cIAI) caused by the following Gram-negative and Gram-positive microorganisms: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZERBAXA and other antibacterial drugs, ZERBAXA should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Important Safety Information about ZERBAXA

Patients with renal impairment: Decreased efficacy of ZERBAXA has been observed in patients with baseline CrCl of 30 to ≤50 mL/min. In a clinical trial, patients with cIAIs with CrCl ≥50 mL/min had a clinical cure rate of 85.2% when treated with ZERBAXA plus metronidazole vs 87.9% when treated with meropenem. In the same trial, patients with CrCl 30 to ≤50 mL/min had a clinical cure rate of 47.8% when treated with ZERBAXA plus metronidazole vs 69.2% when treated with meropenem. A similar trend was also seen in the cUTI trial. Monitor CrCl at least daily in patients with changing renal function and adjust the dose of ZERBAXA (ceftolozane and tazobactam) accordingly.

Hypersensitivity: ZERBAXA is contraindicated in patients with known serious hypersensitivity to ceftolozane/tazobactam, piperacillin/tazobactam, or other members of the beta-lactam class. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. Before initiating therapy with ZERBAXA, make careful inquiry about previous hypersensitivity reactions to cephalosporins, penicillins, or other beta-lactams. If an anaphylactic reaction to ZERBAXA occurs, discontinue use and institute appropriate therapy.

Clostridium difficile–associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including ZERBAXA. Careful medical history is necessary because CDAD has been reported to occur more than two months after the administration of antibacterial agents. If CDAD is confirmed, antibacterial use not directed against C. difficile should be discontinued, if possible.

Development of drug-resistant bacteria: Prescribing ZERBAXA in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse reactions: The most common adverse reactions occurring in ≥5% of patients were headache (5.8%) in the cUTI trial, and nausea (7.9%), diarrhea (6.2%) and pyrexia (5.6%) in the cIAI trial.

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 and connect with us on Twitter, Facebook, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2015 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Please see Prescribing Information for ZERBAXA (ceftolozane and tazobactam) at http://zerbaxa.com/pdf/PrescribingInformation.pdf.

 

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

Merck Nearing FDA Approval For Its Antitoxin (bezlotoxumab) For Prevention Of C. difficile Infection (CDI) Recurrence

Merck  is nearing FDA approval for its Clostridium difficile-fighting antibody, picking up the agency’s priority review designation with the promise of a shortened vetting process.

The FDA accepted Merck’s application for bezlotoxumab and promised to hand down a final decision by July 23, shortening the standard 10-month review to 6 months.

The treatment, licensed from Medarex in 2009, is an antibody designed to block C. difficile toxin B, which damages the gut wall and leads to inflammation that trigger abdominal pain and diarrhea. In Phase III, adding bezlotoxumab to standard of care significantly reduced C. difficile recurrence in high-risk patients after 12 weeks, Merck disclosed in September.

Bezlotoxumab is among the most advanced assets in Merck’s infectious disease pipeline, bolstered by the company’s $9.5 billion buyout of antibiotics specialist Cubist Pharmaceuticals last year. Merck is also at work on therapies for pneumonia, bacterial infection and HIV as it awaits approval for a combination treatment targeting hepatitis C.

 

FULL STATEMENT FROM MERCK:

Merck  known as MSD outside the United States and Canada  January 28, 2016  (today) announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for bezlotoxumab, an investigational antitoxin for prevention of Clostridium difficile (C. difficile) infection recurrence.

The FDA granted Priority Review for bezlotoxumab, with a Prescription Drug User Fee Act (PDUFA) action date of July 23, 2016.

The company also has filed a marketing authorization application for bezlotoxumab with the European Medicines Agency (EMA) that is currently under review.

“Recurrence is a major challenge with C. difficile infection, one of the most common healthcare-associated infections in U.S. hospitals,” said Dr. Roy Baynes, senior vice president of clinical development, Merck Research Laboratories. “Currently, there are no therapies approved for the prevention of C. difficile infection recurrence. As part of Merck’s commitment to the fight against infectious diseases, we look forward to continuing to work with the FDA and EMA to bring forward this novel medicine for appropriate patients.”

The application for bezlotoxumab is based in part on data from the pivota lMODIFY I and MODIFY II clinical trials. Data from these trials were previously presented at the Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC) and International Congress of Chemotherapy and Infection (ICC) 2015 joint meeting.

About bezlotoxumab

Bezlotoxumab is an investigational antitoxin given in conjunction with standard of care antibiotics that are used in the treatment of C. difficile infection. It is not an antibiotic. Bezlotoxumab is designed to neutralize C. difficile toxin B, a toxin that can damage the gut wall and cause inflammation, leading to C. difficile-associated diarrhea.

About Merck

Today’s Merck is 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, visitwww.merck.com and connect with us on TwitterFacebookYouTube and LinkedIn.

Forward-Looking Statement of Merck & Co. Inc., Kenilworth, NJ, USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2014 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

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

http://www.fiercebiotech.com/press-releases/merck-announces-fda-acceptance-biologics-license-application-bezlotoxumab-i

 

AccessDIFICID (fidaxomicin) Is A Support Program For Patients Prescribed DIFICID®

Dificid (fidaxomicin)  Product Access and Support Information:

AccessDIFICID is a support program for patients who have been prescribed DIFICID® (fidaxomicin) tablets.

Case managers are available M-F, 8 am – 8 pm; SAT, 9 am – 1 pm, ET, to provide the following information and support:

  • Research your insurance benefits
  • Obtain information about your out-of-pocket costs
  • Provide information on co-pay assistance options
  • Provide a referral to the Patient Assistance Program (PAP)
  • Provide information about local pharmacies that stock DIFICID and/or options for overnight deliveries of DIFICID, where available, to the location of your choice
  • Answer questions about filling out the AccessDIFICID Enrollment Form

Getting started is simple

  • Download and complete the appropriate sections of the AccessDIFICID Enrollment Form with your health care provider
  • You or your health care provider can fax the completed form to 1-888-997-9329
  • A program representative will then contact you and your health care provider’s office
After your intake form has been processed, you will receive a phone call from an AccessDIFICID case manager, who will work with you throughout the process. You may also contact a case manager at 1-844-282-4782 (M-F, 8 am – 8 pm; SAT, 9 am – 1 pm, ET).

 For continued information for AccessDIFICID please click on the following link:

http://www.accessdificid.com/

 

*The C Diff Foundation does not endorse this or any medical and non-medical treatment available for the
treatment of a C. difficile infection.  All possible treatment options are strictly information
based and for the general public and for general knowledge.   Discuss all treatment options
with the physician/s providing care for and and all diagnosis.  *

C. difficile, a leading Healthcare-Associated Infection, Brings Together World Topic Experts At the International Raising C. diff. Awareness Conference and Health EXPO in Boston, MA on November 9th

 2015 International Raising C. diff. Awareness Conference & Health EXPO

Boston, MA, USA   ~    November 9th

7:30 a.m – 5:00 p.m

conferencesanjuanprJoin us at our 3rd annual International Raising C. diff. Awareness Conference and Health EXPO on November 9th.  Not just another educational conference but one that pairs
world-renowned topic experts with presentations on state-of-the-art health care topics pertaining to a leading Healthcare-Associated Infection (HAI); C. difficile

*Prevention
*Treatments
*Research
*Prevention and Treatment Clinical trials and studies
*Microbiome research
*Infection Prevention
*Environmental Safety
*Fecal Microbiota Restoration and Transplants
……………………..and much more.

The panel of world-renowned topic experts will also discuss the burden of C. diff. the risk factors pertaining to current and emerging treatment options along with the importance of applying evidence-based clinical approaches to the prevention of  a C. diff. infection (CDI), one of the leading Hospital-Acquired Infections.

Clostridium difficile (also known as C. diff.) is an important cause of infectious disease death in the United States.  Nearly half a million Americans suffered from Clostridium difficile (C. diff.) infections in a single year according to a study released February 25, 2015 by the Centers for Disease Control and Prevention (CDC). • More than 100,000 of these infections developed among residents of U.S. nursing homes alone.*  Approximately 29,000 patients died within 30 days of the initial diagnosis of a C. diff. infection.   Of these 29,000 – 15,000 deaths were estimated to be directly related to a  C. diff. infection. Therefore; C. diff. is an important cause of infectious disease death in the U.S.  (Source: CDC)

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Conference Venue:

Double Tree Suites Hotel – Boston – Cambridge
400 Soldiers Field Road, Boston, MA  02134  USA
1-617-783-0090 For Hotel Accommodations *   * There are hotel accommodations available for Sunday evening offered at a special event rate for guests of the C Diff Foundation.  Please inform the DoubleTree representative at the time of creating a reservation to receive the special event room rate.

Exclusive Admission:   $75.00

Student Admission:     $50.00

Each exclusive and student ticket includes admission to all presentations, formal and informal Q&A sessions, introductions to fellow healthcare professionals, continental breakfast  (7:30 a.m.) , a plated four course luncheon with the choice of Chicken Florentine or Petite Filet Mignon main entree, Access to the Health EXPO, a conference book, a educational DVD, and formal conference program.  

To Register and obtain tickets, please click on the following link

NOTE:  *Presentations should not be recorded audio or video or published without prior written and signed permission from the guest speaker and addressed by each attendee seeking publication of said presentations.

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Guest Speakers

Key Speaker and Conference Chair:  Professor Mark Wilcox;  Professor of Medical Microbiology, Leeds Institute of Biomedical and Clinical Sciences, UK. Professor Mark Wilcox is a Consultant Microbiologist, Head of Microbiology and Academic Lead of Pathology at the Leeds Teaching Hospitals, Professor of Medical Microbiology at the University of Leeds, and is the Lead on Clostridium difficile for the Public Health England. He has formerly been the Director of Infection Prevention, Infection Control Doctor and Clinical Director of Pathology at Leeds Teaching Hospitals.

Dr. John Bartlett, MD; Assistant Professor Medicine, UCLA/Sepulveda Veterans Admin Hospital 1972-5, Associate Professor and Professor of Medicine, Tufts University School of Medicine, Boston, 1975-80, Professor of Medicine and Chair Division of Infectious Diseases Division, Johns Hopkins University School of Medicine 1980 – 2006; Professor of Medicine, 2006 – 13; Professor of Medicine emeritus, Johns Hopkins University School of Medicine, 2013.Dominant research interests: anaerobic infections and pulmonary infections 1968 – 74; community acquired pneumonia and diagnostic methods, 1974-1980; Bowel prep for elective colon surgery; Protected bronchoscopy brush catheter-1977; Clostridium difficile 1977 – 84, HIV 1983 – 2014; bioterrorism 1999 –2004; Clostridium difficile infection, HIV/AIDS and antibiotic resistance 2006-2013 with  Major current interests: Clostridium difficile infection, HIV infection, antibiotic resistance, careers in infectious diseases.
Presentation Topic: “The discovery of Clostridium difficile as the cause of antibiotic-associated colitis.”

Professor Simon M. Cutting, Professor of Molecular Microbiology at Royal Holloway, University of London is a bacterial geneticist with over 25 years of experience with Bacillus since graduating from Oxford University with a D. Phil in 1986. His D.Phil was on understanding the genetic control of spore formation in Bacillus. After spending 7 years in the renowned laboratory of Professor Richard Losick at Harvard University Biological Laboratories (USA) he spent 3 years as an Assistant Professor at the University of Pennsylvania Medical School in Philadelphia. He returned to the UK in 1996 and since then has worked on developing bacterial spores as novel oral vaccines at
Royal Holloway, University of London. The Cutting lab has developed a number of prototype oral vaccines and is now entering a ‘first in man’ phase 1/IIa clinical trial of a prototype oral vaccine to 
Clostridium difficile (see www.cdvax.org). His other expertise is in the use of Bacillus spores as probiotics and has a number of contracts and consultancies with European and US companies in the food and feed sectors 
(see SporeGen.com).
Presentation Topic: “Mucosal Vaccination: Decolonisation is Essential to Full Protection Against C. difficile

Dr. Sadeq A. Quraishi, MD, MHA, MMSc   Anesthesiologist/Intensive Care physician in the Department of Anesthesia, Critical Care and Pain Medicine at the Massachusetts General Hospital in Boston, MA. He is also Assistant Professor of Anaesthesia at Harvard Medical School in Boston, MA. Dr. Quraishi’s overall research goal is to better define how macro- and micro-nutrient status influence outcomes during acute stress and critical illness. In particular, his research group has focused on the immunomodulatory effects of vitamin D in the perioperative setting, during acute care hospitalization, and for patients in the intensive care unit. Recently, Dr. Quraishi’s group has identified vitamin D status as a potentially modifiable risk factor for hospital acquired C. diff infections and that the severity of C. Diff infections may also be related to vitamin D status .
Presentation Topic:  “Vitamin D as nutritional immunomodulation
for Clostridium difficile infections.”

Dr. Mary Beth Dorr , Phd, studied Pharmacy at the University of the Sciences in Philadelphia and received a PhD in pharmacokinetics and drug metabolism from the University of North Carolina. For the last 28 years Dr. Dorr has worked in the pharmaceutical industry in various capacities, with the majority of the time devoted to the design and implementation of Phase 1 to 4 clinical trials, primarily for anti-infective products.  Prior to joining Merck, Dr. Dorr directed several large, international clinical studies of the efficacy and safety of two IV antibiotics, Synercid and dalbavancin.  She also directed clinical research programs for gastrointestinal and women’s health products.  Mary Beth joined Merck in February 2011 and is currently a Clinical Director in the Late Stage Clinical Development Department as the Clinical Monitor directing 2 large pivotal Phase 3 trials investigating the safety and efficacy of the monoclonal antibodies actoxumab and bezlotoxumab as adjunctive therapy for the prevention of C. difficile recurrence.
Presentation Topic: Bezlotoxumab for Prevention of Recurrent C. difficile Infection in Patients on Standard of Care Antibiotics:  Results of Phase 3 Trials (MODIFY I and MODIFY II)

Dr. Hudson Garrett, Jr., PhD, MSN, MPH, FNP, CSRN, VA-BC, CDONA,FACONA,DON-CLTC
Dr. Hudson Garrett is currently employed as the VP, Clinical Affairs for PDI and NIce-Pak, and is responsible for the global Clinical Affairs program and also the Medical Science Liaison program for all divisions within the company. He holds a Bachelor of Science degree in Biology/Chemistry and Nursing, a dual Masters in Nursing and Public Health, Post-Masters Certificate as a Family Nurse Practitioner, a Post-Masters Certificate in Infection Prevention and Infection Control and a PhD in Healthcare Administration and Policy. He has completed the Johns Hopkins Fellows Program in Hospital Epidemiology and Infection Control, and the CDC Fundamentals of Healthcare Epidemiology program, and is board certified in family practice, critical care, vascular assess, moderate sedation, legal nurse consulting, and a director of nursing in long term care.  Dr. Garrett is also a Fellow in the Academy of National Associations of Directors of Nursing Administration in Long Term Care.
Presentation Topic:  Preventing Clostridium difficile thru Antibiotic Stewardship

Dr. David Cook, PhD;  A scientist and entrepreneur who has held senior operating and management positions in the biotechnology industry over his 20-year career. Before joining Seres Therapeutics, he was the chief operating officer for the International AIDS Vaccine Initiative, a global R&D organization whose mission is to develop a safe, globally accessible vaccine for HIV. Prior to IAVI, David was the founding CEO at Anza Therapeutics, a biotechnology start-up developing a novel microbial vaccine platform to induce cellular immune responses to fight or prevent diseases such as cancer, hepatitis C, malaria and tuberculosis. He is also a co-inventor on over twenty-five patents. He received his undergraduate degree from Harvard College and his PhD in chemistry from the University of California, Berkeley. Dr Cook is presently Executive Vice President of R&D, Chief Scientific Officer with Seres Therapeutics, Inc.. Presentation Topic: “The role of the microbiome in resisting
C. difficile infection and the mechanism of Ecobiotic drugs.”

Julie Gubb, PhD, CIC,   has worked in the field of Infection Prevention in varying roles at healthcare facilities in multiple states for more than two decades. After graduating from the University of Detroit Mercy with a degree in Medical Technology, she began her career as Senior Clinical Microbiologist at an acute care hospital in Detroit, Michigan, where she developed an interest in Infection Control while managing the activities of a full-service microbiology laboratory. She was the Director of Infection Control at Mount Clemens Regional Medical Center in Michigan, and has also held positions in Infection Prevention at healthcare facilities in California and Nevada. As a Senior Infection Preventionist for Xenex, Julie works closely with hospitals throughout the United States to understand their infection prevention goals and develop strategies for attaining those goals. As an active member of the national organization Association for Professionals in Infection Control & Epidemiology (APIC), she has maintained Board Certification in Infection Control and Epidemiology since 1993 and speaks frequently at APIC chapter meetings.
Presentation Topic: Stand Up for Cleanliness / Enhanced Room Disinfection

Dr. Patricia J. Freda Pietrobon, PhD: Associate Vice President, R&D,
Sanofi Pasteur, has over 25 years of experience in the Vaccine & Diagnostic industries and more then 20 years in leadership roles focusing on research & development of new vaccines. Patricia began her career in diagnostic assay development with a focus on validation and quality alignment to regulatory requirements and GXPs. Patricia has been with Sanofi Pasteur for over 25 years and has contributed to the development and licensure of new bacterial & viral vaccines for pediatric & adult populations worldwide.

Barley Chironda, Manager of Infection Prevention and Control (IPAC) and Medical Device Reprocessing Device at St. Joseph Health Centre in Toronto, Canada. He is certified in Infection prevention and control (CIC TM) and has worked extensively as an Infection Preventionist. Barely has been an integral to the successful decline in Clostridium difficile infections through implementing innovative technology and quality improvement behavioral changes.   Barley’s presentation will show a behind the scenes account of the C. diff. management from the healthcare facilities perspective while providing a call to action.

Dr. Martha Clokie, PhD, Leicester UK, Professor in Microbiology.  Dr. Cloakie’s research focuses on phages that infect bacterial pathogens of medical relevance and  has published 41 papers in this area. Her major focus has been on Clostridium difficile where she has  isolated a large phage collection. In vitro and in vivo data has shown that the viruses have therapeutic potential. A patent has been filed  on these phages and  working with AmpliPhi to develop a product. Dr. Cloakie  has regular contact with the BBC and other media to talk about her work, and other phage projects, and has consulted with Science museum, London and Eden Project, UK to advise on bacteriophage displays.

Lee Jones, Founder, President and CEO of Rebiotix Inc, has over thirty years of experience in the medical technology industry in large and small companies and academia. Most recently Lee was Chief Administrative Officer of the Schulze Diabetes Institute at the University of Minnesota, Minneapolis, MN and is the former president and chief executive officer of Inlet Medical. Inlet Medical was sold to Cooper Surgical in 2006. Lee will introduce Rebiotix Inc.,  a biotechnology company founded in 2011 in Roseville, MN to revolutionize the treatment of challenging gastrointestinal diseases by harnessing the power of the human microbiome The company is developing an entirely new kind of biological drug designed to reverse pathogenic processes responsible for disease through the transplantation of live human-derived microbes into a sick person’s intestinal tract.
Presentation Topic:  Blazing a Trail with the Gut Microbiome

Professor Nancy Sheridan,   a C. diff. Survivor and  Associate Professor at the Fashion Institute of Technology and a winner of the prestigious SUNY Chancellor’s Award for Excellence in Teaching. Professor Sheridan will share her personal experience being treated for a painful and extended journey with a C. diff. infection (CDI).  Professor Sheridan has been teaching since fall 2000 in the Fashion Merchandising Management Department within the School of Business and Technology. For the past seven years, she has also taught at the University of Pennsylvania, Wharton Business School to undergraduate and MBA students.

Dr Mel Thomson, PhD,  completed her Honors degree in microbiology and immunology at the University of Melbourne . She then immigrated to the UK where she worked on various projects as diverse as allergy and cancer before undertaking further studies. She completed a Masters of Research in functional genomics before reading for a PhD in microbial genetic regulation in Neisseria species, both at University of York, UK. After the award of her PhD, Dr Thomson became interested the host-pathogen interactions at the Leeds Institute of Molecular Medicine, UK.  Dr Thomson returned to Australia in 2011 to start her own research group studying host-pathogen interactions in the GI tract, at Deakin Medical School. A passionate science communicator, and has recently become a national ‘torch bearer’ for the concept of crowd funding academic research, which a track record of three successful ‘Pozible’ crowd funding campaigns, ‘Mighty Maggots’, ‘Hips 4 Hipsters’ and ‘No more Poo Taboo’
Presentation Topic: All that glitters is C.diff awareness gold and Crowdfunding: The ‘No more poo taboo’ animation”

Dr Rahma Wehelie – LifeClean International AB – Sweden; LifeClean International AB is a Swedish company with an international orientation that conducts research, development, and production in the spore, bacteria, and virus eliminating industry. LifeClean was established in 2013 after many years of research and the headquarter lies in Uddevalla, Sweden.
Presentation Topic: Dr Wehelie will be discussing LifeClean’s research, development and production eliminating Clostridium difficile, Norovirus, and other multidrug-resistant bacteria

Dr. Klaus Gottlieb, MD, FACG,Synthetic Biologics, Inc.,Vice President, Clinical;Regulatory Affairs   Dr. Gottlieb is an experienced board-certified internist and gastroenterologist with a strong clinical science, business and drug development background. He joined Synthetic Biologics after serving as Senior Medical Director-Therapeutic Strategy Lead Gastroenterology of Quintiles, a Fortune 500 company and the world’s largest provider of biopharmaceutical development and commercial outsourcing services. At Quintiles, Dr. Gottlieb served as Global Medical Advisor for three separate large Phase 3 inflammatory bowel disease (IBD) trials and provided significant input on the shaping, design and evaluation of numerous IBD and other gastrointestinal (GI) clinical trials throughout all stages of development programs. Prior to joining Quintiles in 2013, he was with the FDA in Silver Spring, MD as a Senior Clinical Reviewer for the Division of Gastroenterology and Inborn Errors Products. Widely published, his academic contributions have been recognized by an appointment as Professor of Medicine (Clinical) at George Washington University and the following elected fellowships: Fellow American College of Physicians, Fellow American College of Gastroenterology, Fellow American Society of Gastrointestinal Endoscopy.  Presentation Topic: Protecting the Gut Microbiome

For additional information contact the C Diff Foundation: (919) 201-1512 or
info@cdifffoundation.org

To Register and obtain tickets, please click on the following link

We would like to sincerely thank the following Exclusive and Supporting Corporate Sponsors for their continued support  and joining the Foundation in
Raising C. diff. Awareness worldwide.

  • Enjoy visiting our Exclusive Corporate Sponsors websites by simply clicking on their logos belowsyntheticbiologics
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SANOFI_Pasteur_RVBThis conference is supported through an educational grant from Sanofi Pasteur US

 

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advocacy grant from Merck & Co., Inc.

Merck’s Phase 3 Studies of Bezlotoxumab, its Investigational Antitoxin to Prevent C. difficile Recurrence Met Primary Endpoint

NewspaperIIIN THE NEWS

Merck  known as MSD outside the United States and Canada, announced that the two pivotal Phase 3 clinical studies for bezlotoxumab, its investigational antitoxin for prevention of Clostridium difficile (C. difficile) infection recurrence, met their primary efficacy endpoint: the reduction in C. difficile recurrence through week 12 compared to placebo, when used in conjunction with standard of care antibiotics for
the treatment of C. difficile.

Based on these results, the company plans to submit new drug applications seeking regulatory approval of bezlotoxumab in the U.S., EU and Canada in 2015. Currently, there are no therapies approved for the prevention of recurrent disease caused by C. difficile.

“These results were also demonstrated in patient subgroups known to be at
high risk for C. difficile recurrence.”

Results from the studies were presented for the first time at the Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC) and International Congress of Chemotherapy and Infection (ICC) joint meeting in San Diego, Sept. 17-21.

“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 Dr. Mark Wilcox, Leeds Teaching Hospitals and University of Leeds, U.K., and a lead investigator for the studies. “These results were also demonstrated in patient subgroups known to be at high risk for C. difficile recurrence.”

Bezlotoxumab is not an antibiotic. It is a selective, fully-human, monoclonal antibody designed to
neutralize C. difficile toxin B, a toxin that can damage the gut wall and cause inflammation, leading to the symptoms of C. difficile enteritis, which include abdominal pain and watery diarrhea.

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 licensed to Merck in 2009 for development as a potential
therapeutic for C. difficile infection.

“Recurrence is a major challenge with C. difficile infection, and novel approaches are
needed to help prevent the cycle of C. difficile recurrence,” said Dr. Dale Gerding, professor of medicine, Loyola University Chicago Stritch School of Medicine, Maywood, Ill., and a lead investigator for the studies.

About the pivotal Phase 3 studies

Two global, Phase 3, double-blind studies were conducted to evaluate bezlotoxumab, either alone or in combination with actoxumab (a fully human monoclonal antibody against C. difficile toxin A), compared to placebo for the prevention of recurrent C. difficile infection in patients on standard of care antibiotics for a primary or recurrent C. difficile infection. The MODIFY I study (MONOCOLONAL ANTIBODIES FOR C. DIFFICILE THERAPY) enrolled 1452 patients (median age 65 years) in 19 countries and the MODIFY II study enrolled 1203 patients (median age 67 years) in 17 countries. The studies were conducted in both hospital and outpatient settings, and the primary endpoint for each study was evaluated through 12 weeks following study drug administration.

In the MODIFY I study, patients receiving standard of care antibiotics for C. difficile were randomized to receive a single, one-time infusion of either bezlotoxumab (10 mg/kg) (n=403), actoxumab (10 mg/kg) (n=242), the combination of bezlotoxumab and actoxumab (10 mg/kg each) (n=403) or placebo (n=404). The actoxumab arm was stopped for efficacy and safety reasons after an interim analysis. In the MODIFY II study, patients receiving standard of care antibiotics for C. difficile were randomized to receive a single, one-time infusion of either bezlotoxumab (10 mg/kg) (n=407), bezlotoxumab and actoxumab (10 mg/kg each) (n=397) or placebo (n=399).

In both MODIFY I and MODIFY II, the rate of C. difficile infection recurrence through week 12, the primary efficacy endpoint, was significantly lower in the bezlotoxumab arms (17.4%, p=0.0003) and (15.7%; p=0.0003), and the combination bezlotoxumab and actoxumab arms (15.9%, p<0.0001) and (14.9%, p<0.0001), compared to the placebo arms (27.6%) and (25.7%), respectively. In MODIFY I and MODIFY II, 1396 and 1163 patients were evaluated in the full analysis sets, respectively.

In both studies, the rate of C. difficile infection recurrence was lower in the bezlotoxumab arms compared to the placebo arms in patient subgroups known to be at high
risk for C. difficile recurrence, including patients with any prior
episode(s) of C. difficile infection within the previous six months, patients infected with the BI/NAP1/027 strain, patients with severe C. difficile infection (Zar score ≥ 2), patients 65 years of age or older, and patients with compromised immunity. These subpopulation analyses were pre-specified in the protocol for each study.

In the studies, the adverse reaction rates were comparable across the bezlotoxumab and placebo arms. In MODIFY I, the most common adverse reactions through four weeks after infusion (nausea, diarrhea and pyrexia) occurred at similar rates in the bezlotoxumab group (7.4%, 6.7% and 5.6%) and the placebo group (6.5%, 5.0% and 2.8%). In MODIFY II, the most common adverse reactions through four weeks after infusion (nausea, diarrhea and urinary tract infection) occurred at similar rates in the bezlotoxumab group (5.8%, 5.3% and 4.5%) and the placebo group (3.4%, 6.6% and 4.2%). Additionally, rates of serious adverse reactions and deaths assessed through 12 weeks after infusion were comparable across these treatment arms.

Treatment with the combination of bezlotoxumab and actoxumab did not provide added efficacy over bezlotoxumab alone. Furthermore, actoxumab alone provided no benefit in the prevention of C. difficile recurrence compared with placebo. Based on these results, bezlotoxumab alone was selected for the marketing authorization application.

About Merck

Today’s Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside of 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 healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

 

To read the article in its entirety click on the following link:

http://www.businesswire.com/news/home/20150920005053/en/Pivotal-Phase-3-Studies-Bezlotoxumab-Merck%E2%80%99s-Investigational#.VgFWTpftVQs

 

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