The challenges raised by the pathologic strains of Clostridium difficile, and the failure of current treatments to contain infection recurrence, is the reason for our enthusiasm about the positive results from the second part of phase 3 trials with Optimer’s (NASDAQ:OPTR) drug Fidaxomicin. The wonder drug is also known as OPT-80, and it has shown to be especially effective on infection recurrence.
High on our long list of expectations from the biotechnology industry are far-reaching antibiotics for infections which have a tendency to recur after successful treatments, or to develop resistance to antibiotics. Clostridium difficile organisms overrun their environment in the intestines, become infective, and are tough to erase, often recurring.
This bacterium, which resides naturally in the body, is usually harmless. Only when it becomes overpopulated, it turns pathological. Several factors cause the transformation. These include: long-term hospitalization, widespread use of broad-spectrum antibiotics, as well as medications that suppress gastric acid production, such as H2-receptor antagonists and proton pump inhibitors.
As it becomes overpopulated, C. difficile causes disagreeable symptoms, including bloating, diarrhea and abdominal pain, which may become intolerable. Flu-like symptoms then appear and pseudomembranous colitis (an infection inflammation of the colon) occurs with the development of pseudomembrane, a viscous collection of inflammatory cells, fibrin, and necrotic cells. The pathogenic C. difficile strains then produce toxins. It is said that C. difficile infection (CDI) consequences can range from asymptomatic to life-threatening, especially among the elderly.
Antibiotic treatment of C. difficile infections is difficult, since heat-resistant spores form. The spores also enable infection in hospitals and nursing homes to remain for long periods of time, contaminating new patients and re-contaminating those who came to be treated in the first place.
Disinfectants generally used in hospitals are ineffective against the spores and may actually promote more spore formation. There are no preventive vaccines, and attempts to use non-pathogenic bacterial flora such as lactobacilli and Saccharomyces boulardi as prophylactic has had minor success in preventing relapse.
Current treatments: Metronidazole and vancomycin have been the mainstays of therapy for Clostridium difficile–associated disease (CDAD) for 25 years. Metronidazole is said to be chosen as initial treatment for reasons related to cost. Vancomycin, however, is considered the most effective treatment and is recommended for first-line therapy in severe cases.
On the downside, some studies show that hyperproduction of toxin by the outbreaks of severe disease associated with a hypervirulent BI/NAP1/027 subtype C. difficile strains might render vancomycin relatively less effective because overwhelming amounts of toxin already have bound to receptors by the time the drug reaches the colon. A major problem remaining is the frequent recurrence of infection.
These challenges are what kindles our hope for more effective breakthrough drugs, or drugs that can prevent infection recurrence to emerge from the biotechnology industry’s labs. In the past week, results of second phase 3 clinical study in patients with Clostridium difficile infection (CDI) were presented at the 20th Annual European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Vienna, Austria. These results poured a new energy in our hopes. Fidaxomicin has met the primary endpoint of non-inferiority in clinical cure compared to Vancocin.
Optimer’s drug had significantly lower recurrence rates compared to Vancocin (p = 0.002), and significantly higher global cure rates (defined as cure with no recurrence within four weeks of completing therapy) compared to Vancocin (p < 0.001). Is this not what we are looking for? Even more comforting is the fact that the trials were the largest comparative studies ever conducted against Vancocin in CDI. They enrolled more than 1,100 subjects.
According to Dr. Crook, M.D., Consultant Microbiologist/Infectious Diseases and Professor of Infectious Diseases and Microbiology, Experimental Medicine Division, Nuffield Department of Clinical Medicine (NDM), University of Oxford, fidaxomicin provided an improvement in recurrence rates compared to the currently approved treatment even in patients with the hypervirulent BI/NAP1/027 subtype.
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