The US Food and Drug Administration (FDA) has approved bezlotoxumab (Zinplava™, Merck) injection to reduce the recurrence of Clostridium difficile infection (CDI) in patients aged 18 years or older who are receiving antibacterial treatment of CDI and are at high risk for CDI recurrence.1  

In June 2016, the FDA’s Antimicrobial Drugs Advisory Committee voted 10-5 to recommend the approval of bezlotoxumab based on the presentation of substantial evidence to support its safety and efficacy in patients aged ≥18 years.2 It was also granted Priority Review for its Biologics License Application (BLA) in January 2016.

Bezlotoxumab is a human monoclonal IgG1/kappa antibody that binds to C difficile toxin B and neutralizes its effects. It inhibits the binding of toxin B and prevents its effects on mammalian cells; it does not bind to C difficile toxin A. It is not an antibacterial drug and should only be used in conjunction with antibacterial treatment of CDI.

The safety and efficacy of bezlotoxumab were investigated in two randomized, double-blind, placebo-controlled, multicenter, phase 3 trials (Trial 1, ClinicalTrials.gov Identifier NCT01241552 and Trial 2, ClinicalTrials.gov Identifier NCT01513239) in patients receiving standard of care antibacterial drugs for treatment of CDI (metronidazole, vancomycin, or fidaxomicin).  Sustained clinical response was defined as clinical cure of the presenting CDI episode and no CDI recurrence through 12 weeks after infusion. 

In Trial 1, 60.1% of patients in the bezlotoxumab arm had sustained clinical response compared to 55.2% in the placebo arm. In Trial 2, 66.8% of bezlotoxumab-treated patients had sustained clinical response versus 52.1% in the placebo group.

Heart failure was reported more commonly in the two Phase 3 clinical trials in bezlotoxumab-treated patients compared to placebo-treated patients. These adverse reactions occurred primarily in patients with underlying congestive heart failure (CHF). In patients with a history of CHF, bezlotoxumab should be reserved for use when the benefit outweighs the risk.

Bezlotoxumab Injection will be available as a 25mg/mL (1,000mg/40mL) strength preservative-free solution in single-dose vials. It is anticipated to launch in the first quarter of 2017.

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Reference

  1. Zinplava™ [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2016.
  2. US Food and Drug Administration. FDA briefing document of bezlotoxumab injection: meeting of the antimicrobial drugs advisory committee (AMDAC). http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM505290.pdf. Updated June 9, 2016. Accessed October 25, 2016. 

This article originally appeared on MPR