Approval Status: Approved October 2016
Specific Treatments: recurrent Clostridium difficile infection in patients receiving antibacterial treatment
Zinplava (bezlotoxumab) is a human monoclonal antibody that binds to C. difficile toxin B and neutralizes its effect.
Zinplava is specifically 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 a high risk for CDI recurrence.
Zinplava is supplied as an injection for intravenous infusion. The recommended dose is a single dose of 10 mg/kg administered as an intravenous infusion over 60 minutes. Zinplava must be diluted prior to intravenous infusion. Please see drug label for specific instructions.
The FDA approval of Zinplava was based on two phase III trials. MODIFY I and II. MODIFY I enrolled 1,452 patients (median age 65 years) in 19 countries and the MODIFY II study enrolled 1,203 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 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.
Adverse effects associated with the use of Zinplava may include, but are not limited to, the following:
In addition, heart failure was reported more commonly in Zinplava-treated patients with a history of congestive heart failure (CHF) in the two Phase III clinical trials. In patients with a history of CHF, Zinplava should be reserved for use when the benefit outweighs the risk.
Mechanism of Action
Zinplava (bezlotoxumab) is a human monoclonal antibody that binds C. difficile toxin B with an equilibrium dissociation constant (Kd) of <1×10-9M. Bezlotoxumab inhibits the binding of toxin B and prevents its effects on mammalian cells. Bezlotoxumab does not bind to C. difficile toxin A.
For additional information regarding Zinplava or recurrent Clostridium difficile infection (CDI) in patients 18 years of age or older who are receiving antibacterial drug treatment of CDI and are at a high risk for CDI recurrence, please visit http://www.zinplava.com/