Bezlotoxumab (Zinplava) Form

Bezlotoxumab (Zinplava™) is a human monoclonal antibody that binds to Clostridium difficile toxin B. FDA Approved Indication(s) Zinplava is indicated to reduce recurrence of Clostridioides difficile infection (CDI) in adults and pediatric patients 1 year of age and older who are receiving antibacterial drug treatment for CDI and are at a high risk for CDI recurrence. Limitation(s) of use: 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. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Zinplava is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Clostridium difficile Infection (must meet all):

1. Diagnosis of CDI confirmed by documentation of positive Clostridium difficile test;
   2. Age ≥ 1 year;
   3. Member will receive or is currently receiving concomitant antibacterial drug treatment for CDI (e.g., vancomycin, fidaxomicin);
2. Member has had at least one episode of CDI recurrence (total 2 episodes) in the previous 6 months and has been treated with appropriate treatment for CDI (e.g., vancomycin, fidaxomicin), including a pulsed vancomycin regimen; *Treatment failure for CDI may be declared in as little as 48 hours in patients with severe disease who fail to improve.
3. Dose does not exceed 10 mg/kg once. Approval duration: 3 months (1 dose only)
   B. Other diagnoses/indications (must meet 1 or 2):

4. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): Page 1 of 7

   CLINICAL POLICY Bezlotoxumab a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

5. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Clostridium difficile Infection
6. Re-authorization is not permitted. Members must meet the initial approval criteria. Approval duration: Not applicable B. Other diagnoses/indications (must meet 1 or 2):
7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

8. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid or evidence of coverage documents.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CDI: Clostridium difficile infection Page 2 of 7

   CLINICAL POLICY Bezlotoxumab FDA: Food and Drug Administration IDSA: Infectious Diseases Society of America Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Dosing Regimen Drug Name Dose Limit/ Maximum Dose See regimen See regimen Dificid® (fidaxomicin)
   vancomycin 200 mg PO BID for 10 days; for recurrences, may use alternative regimen of 200 mg PO BID for 5 days, followed by QOD for 20 days Adult: 125 mg PO QID for 10 days; for recurrences, may use a tapered and pulsed regimen Pediatric: 10 mg/kg/dose PO QID Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • The new term Clostridioides difficile was introduced in 2019. It may be used interchangeably with Clostridium difficile.
   • Zinplava is the only medication approved to reduce the recurrence of CDI. • Zinplava was studied in two randomized placebo controlled trials in which patients received a single IV infusion of Zinplava. The efficacy of repeat courses of Zinplava therapy has not been established. • Approximately 35% of CDI patients experience recurrence after the initial treatment and resolution of diarrhea. Of those who have a primary recurrence, 40% will have another CDI episode, and after 2 recurrences, the chance of an additional episode increases to as high as 65%.
   • Per the IDSA Clinical Practice Guidelines for Clostridium difficile Infection 2017 Update: o An incident case is one with a new primary symptom onset (i.e., in the previous 8 weeks, there was not an episode of positive symptoms with positive C. diff result) and positive C. diff assay result.
   o A recurrent infection is an episode of symptom onset with a positive assay result following an episode with positive assay result in the previous 2–8 weeks. • Per the IDSA 2021 Focused Update for Clostridium difficile Infection in adults: o Fidaxomicin (standard or extended-pulsed regimen) is the preferred first-line treatment for patients with recurrent CDI episode(s). Page 3 of 7

   CLINICAL POLICY Bezlotoxumab o Vancomycin in a tapered and pulsed regimen or as a standard course are acceptable alternatives for first CDI recurrence. For patients with multiple recurrences, vancomycin in a tapered and pulsed regimen, vancomycin followed by rifaximin, and fecal microbiota transplantation are options in addition to fidaxomicin.
   • Examples of treatment regimens for recurrence: o Adult: Vancomycin 125 mg PO QID for 10 days (may be followed by rifaximin 400 mg PO TID for 20 days)
   o Pediatric: Vancomycin 10 mg/kg PO QID for 10 days (may be followed by rifaximin* for 20 days)

   • rifaximin is not FDA-approved for use in children <12 years of age o Tapered and pulsed regimens of vancomycin (e.g., vancomycin PO 125 mg QID for 10 to 14 days, then BID for 1 week, then QD for 1 week, then every 2 or 3 days for 2 to 8 weeks) o Adult: Fidaxomicin 200 mg PO BID for 10 days o Adult: Fidaxomicin 200 mg PO BID for 5 days followed by once every other day for 20 days o Fecal microbiota transplantation V. Dosage and Administration
     Indication CDI recurrence Dosing Regimen 10 mg/kg as a single dose IV infusion over 60 minutes Maximum Dose 10 mg/kg VI. Product Availability
     Single-dose vial for injection: 1,000 mg/40 mL (25 mg/mL) VII.