An important new treatment aimed at fighting a recurrent type of infection frequently affecting older people in community health care and nursing home settings – Clostridium difficile – has passed a milestone in clinical studies and is due to be submitted for approval.
C. difficile causes recurrent intestinal infection.
Bezlotoxumab is not an antibiotic but a “selective, fully-human, monoclonal antibody designed to neutralize C. difficile toxin B,” according to Merck, the international pharmaceutical company with the license to develop it.
Bezlotoxumab is based on discoveries made at the University of Massachusetts Medical School (UMMS) MassBiologics, in conjunction with Medarex. It was licensed to Merck in 2009 for development.
C. difficile is one of a group of diseases of growing concern – known as health care-associated infections (HAIs). It is a notoriously recurrent infection, the incidence of which has risen sharply over the last 20 years.
Toxin B is the toxin which causes the infection. Toxin B damages the intestinal wall and causes inflammation. This leads to the symptoms of C. difficile, including abdominal pain and watery diarrhea.
Older people are largely affected, and those whose immune systems are compromised due to underlying disease or treatment. Recurrence is a major problem, with approximately 1 in 4 patients experiencing recurrence after an initial bout, and 40% of those people going on to have further recurrences.
In 2011, C. difficile affected almost half a million people in the US, killing 29,000, of whom 8 out of 10 were over 65. Fatalities often occur within 30 days of initial diagnosis.
No effective therapy is currently approved for treating C. difficile. Certain types of antibiotics and other medications often cause the infection, and the Centers for Disease Control and Prevention (CDC) recommend reviewing or discontinuing antibiotic use once the infection appears in order to help control it. It is hoped that the new antibody will help.
Merck say that studies for bezlotoxumab have achieved their primary efficiency endpoint, and that the antibody is ready for the next stage of development. Results so far look promising.
Significant reduction in recurrence as a result of bezotoxumab
Two studies were conducted to evaluate bezlotoxumab. The first involved 1,452 patients in 19 countries, with a median age of 65 years. The second study involved 1,203 patients with a median age of 67 years in 17 countries. The studies were carried out in hospitals and outpatient settings.
Fast facts about C. difficile
- C. difficile bacteria is not killed by hand sanitizer; gloves must be worn in health care settings to help prevent infection
- Patients should be screened for infection on admission to the hospital
- Patients on antibiotics are 7-10 times more likely to contract it.
Learn more about C. difficile
The patients were given either a single, one-time infusion of bezlotoxumab alone or bezlotoxumab plus actoxumab, – which is a monoclonal antibody for treating C. difficile Toxin A – or a placebo.
Where bezlotoxumab or bezotoxumab plus actoxumab was taken, infection recurrence was significantly lower compared with the placebo. The benefit was demonstrated over a 12-week period.
According to Merck, in the tests, the combined bezlotoxumab and actoxumab treatment was no more effective than bezlotoxumab alone, and actoxumab alone did not provide any benefit compared with the placebo.
Therefore, bezlotoxumab alone was selected for the marketing authorization application. The application will be submitted in 2015 and will seek regulatory approval for the antibody in the US, Europe and Canada.
Lead investigator Dr. Mark Wilcox, of Leeds Teaching Hospitals and the University of Leeds in the UK, comments that during the trials, bezlotoxumab given with the standard of care C. difficile antibiotic treatment significantly reduced the recurrence of C. difficile infection compared with standard of care alone. He also points to its effectiveness among patients 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.
Dr. Mark Klempner, UMass Medical School’s executive vice chancellor for MassBiologics, says:
“Discovering and developing effective new treatments for significant public health threats is the mission of MassBiologics.We are pleased that these two pivotal clinical trials form the basis for Merck to submit a new biologics license application seeking regulatory approval in the US, as well as applications in Europe and Canada.”
MassBiologics are the only nonprofit manufacturer of vaccines in the US which is licensed by the Food and Drug Administration (FDA). They have specialized in applied biologics for over 100 years and produce vaccines, plasma derivatives and most recently, monoclonal antibodies.
Merck operate in more than 140 countries to deliver innovative health solutions, describing themselves as “a global health care leader working to help the world be well.”
In May 2015, Medical News Today reported on a treatment for C. difficile infection that involved the administration of a nontoxic strain of the bacteria.
Written by Yvette Brazier
Copyright: Medical News Today
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