ZINPLAVA™

(bezlotoxumab) injection 25 mg/mL

Efficacy Profile

Help take control with ZINPLAVA: Reduce CDI recurrence in high-risk adult patients receiving CDI antibiotics


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Adding ZINPLAVA helped patients to achieve sustained clinical response* vs SoC antibiotics alone


In clinical trials, ZINPLAVA sustained the clinical response

  • Sustained clinical response results (ZINPLAVA + SoC CDI antibiotics vs Placebo + SoC CDI antibiotics):
    • MODIFY I : 60.1% vs 55.2% (95% CI: 4.8 [-2.1, 11.7])
    • MODIFY II : 66.8% vs 52.1% (95% CI: 14.6 [7.7, 21.4])
  • * Sustained clinical response was defined as clinical cure of the presenting CDI episode and no CDI recurrence through 12 weeks after infusion.

Adding ZINPLAVA reduced CDI recurrence through 12 weeks of treatment1

Recurrent Episodes Through 12 Weeks of Treatment for C. Difficile Infection The Full Analysis Set was a subset of all randomized subjects with exclusions for: (i) not receiving infusion of study medication; (ii) not having a positive local stool test for toxigenic C. difficile; (iii) not receiving protocol-defined SOC therapy within a 1-day window of the infusion.

aComparisons between treatment and placebo with regard to the primary end point were performed at a two-sided alpha level of 0.025 in MODIFY I.1

bComparisons between treatment and placebo with regard to the primary end point were performed at a two-sided alpha level of 0.050 in MODIFY II.1


  • In MODIFY I, the clinical cure rate of the presenting CDI episode was lower in the ZINPLAVA plus SoC CDI antibiotics arm compared to placebo plus SoC CDI antibiotics arm. In MODIFY II, the clinical cure rate was lower in the placebo plus SoC CDI antibiotics arm compared to the ZINPLAVA plus SoC CDI antibiotics arm.
  • Additional analyses showed that by 3 weeks poststudy drug infusion, the clinical cure rates of the presenting CDI episode were similar between treatment arms.
  • Patients in the ZINPLAVA and placebo arms who did not achieve clinical cure of the presenting CDI episode received a mean of 18 to 19 days of SoC and had a mean of 4 additional days of diarrhea following completion of SoC.

Study design

Efficacy and safety of ZINPLAVA were investigated in 2 randomized, double-blind, placebo-controlled, multicenter Phase 3 trials in 1,554 adult patients. Enrolled patients had a confirmed diagnosis of CDI, defined as diarrhea (≥3 loose bowel movements in ≤24 hours) and a positive stool test for toxigenic C. difficile from a stool sample collected ≤7 days before study entry. Patients received a 10- to 14-day course of oral CDI antibiotics (metronidazole, vancomycin, or fidaxomicin). Patients were randomized to receive either a single 10-mg/kg (body weight) IV infusion of ZINPLAVA (n=781) or placebo IV (n=773) during the course of the CDI antibiotic therapy. Patients were assessed for clinical cure of the presenting CDI episode, defined as no diarrhea for 2 consecutive days following the completion of a ≤14-day CDI regimen. Patients who achieved clinical cure were then assessed for recurrence of CDI through 12 weeks following administration of the infusion of ZINPLAVA or placebo.

Definitions

CDI = Clostridium difficile infection 

CI = confidence interval 

IV = intravenous 

NS = not significant 

RRR = relative risk reduction 

SoC = standard of care

References

1. Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376(4):305–317. doi:10.1056/NEJMoa1602615 

2. Data available on request from Merck & Co, Inc., Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package US-MKB-00157.

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Indication

ZINPLAVA is a human monoclonal antibody that binds to Clostridium difficile toxin B 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 high risk for CDI recurrence.

ZINPLAVA is not indicated for the treatment of CDI. ZINPLAVA is not an antibacterial drug. ZINPLAVA should only be used in conjunction with antibacterial drug treatment of CDI.

Selected Safety Information

  • In patients with a history of congestive heart failure (CHF), ZINPLAVA should be used when the benefit outweighs the risk. Heart failure was reported more commonly in the two Phase 3 clinical trials in ZINPLAVA-treated patients compared to placebo-treated patients. In patients with a history of CHF, 12.7% (n=15/118) of ZINPLAVA-treated patients and 4.8% (n=5/104) of placebo-treated patients had the serious adverse reaction of heart failure during the 12-week study period. During the same period, for patients with a history of CHF, there were more deaths in ZINPLAVA-treated patients 19.5% (n=23/118) than in placebo-treated patients 12.5% (n=13/104). The causes of death varied and included cardiac failure, infections, and respiratory failure.
  • The most common adverse reactions occurring within 4 weeks of infusion with a frequency greater than placebo and reported in ≥4% of patients treated with ZINPLAVA and Standard of Care (SoC) antibacterial drug therapy vs placebo and SoC antibacterial drug therapy were nausea (7% vs 5%), pyrexia (5% vs 3%), and headache (4% vs 3%).
  • Serious adverse reactions occurring within 12 weeks following infusion were reported in 29% of ZINPLAVA-treated patients and 33% of placebo-treated patients. Heart failure was reported as a serious adverse reaction in 2.3% of the ZINPLAVA-treated patients and 1.0% of placebo-treated patients.
  • In ZINPLAVA-treated patients, 10% experienced one or more infusion specific adverse reactions compared to 8% of placebo-treated patients, on the day of or the day after, the infusion. Infusion specific adverse reactions reported in ≥0.5% of patients receiving ZINPLAVA and at a frequency greater than placebo were nausea (3%), fatigue (1%), pyrexia (1%), dizziness (1%), headache (2%), dyspnea (1%), and hypertension (1%). Of these patients, 78% experienced mild adverse reactions, and 20% experienced moderate adverse reactions. These reactions resolved within 24 hours following onset.
  • As with all therapeutic proteins, there is a potential for immunogenicity following administration of ZINPLAVA. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Comparison of the incidence of antibodies to bezlotoxumab in the two Phase 3 studies (MODIFY I and II) with the incidence of antibodies in other studies or to other products may be misleading. In MODIFY I and II, none of the 710 evaluable ZINPLAVA-treated patients tested positive for treatment-emergent anti-bezlotoxumab antibodies.

Before prescribing ZINPLAVATM (bezlotoxumab), please read the Prescribing Information. The Patient Information also is available.

US-MKB-0055107/21