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FDA Approves Zinplava to Reduce Recurrence of Clostridium difficile Infection
The FDA has given the green light to bezlotoxumab (Zinplava, Merck), a monoclonal antibody indicated to reduce the 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. Bezlotoxumab is not indicated for the treatment of CDI and is not an antibacterial drug. Bezlotoxumab should be used only in conjunction with antibacterial drug treatment of CDI.
The product is expected to be available in the first quarter of 2017.
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.
Bezlotoxumab was developed by researchers at the University of Massachusetts Medical School in conjunction with Medarex (now part of Bristol-Myers Squibb), and was licensed to Merck in 2009.
Heart failure was reported more often in bezlotoxumab-treated patients compared with placebo-treated patients in two phase 3 studies. This adverse event occurred primarily in patients with underlying congestive heart failure (CHF). In patients with a history of CHF, 12.7% (15/118) of bezlotoxumab -treated patients and 4.8% (5/104) of placebo-treated patients experienced heart failure during the 12-week study period. In addition, in patients with a history of CHF, there were more deaths among bezlotoxumab-treated patients (19.5% [23/118]) than among placebo-treated patients (12.5% [13/104]) during the 12-week study period. The causes of death included cardiac failure, infections, and respiratory failure. In patients with a history of CHF, bezlotoxumab should be reserved for use when the benefit outweighs the risk.
The most common adverse events occurring within four weeks of infusion with bezlotoxumab in addition to standard-of-care (SoC) antibacterial drug therapy compared with placebo and SoC antibacterial drug therapy included nausea (7% vs. 5%, respectively), pyrexia (5% vs. 3%), and headache (4% vs. 3%).
Serious adverse events occurring within 12 weeks after infusion were reported in 29% of bezlotoxumab-treated patients and in 33% of placebo-treated patients. Heart failure was reported as a serious adverse event in 2.3% of bezlotoxumab-treated patients and in 1.0% of placebo-treated patients.
As with all therapeutic proteins, there is a potential for immunogenicity after the administration of bezlotoxumab. The detection of antibody formation depends on the sensitivity and specificity of the assay. In addition, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, the 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. After treatment with bezlotoxumab in these two studies, none of the 710 evaluable patients tested positive for treatment-emergent anti-bezlotoxumab antibodies.
Source: Merck; October 21, 2016.