Nadofaragene Firadenovec (Instiladrin) Form

Nadofaragene firadenovec-vncg (Adstiladrin®) is a gene therapy via a non-replicating adenovirus vector harboring the human interferon alpha2b gene.
FDA Approved Indication(s)
Adstiladrin is indicated for the treatment of adult patients with high-risk, Bacillus Calmette- Guerin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. 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 Adstiladrin is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Non-Muscle Invasive Bladder Cancer (must meet all):

1. Diagnosis of NMIBC characterized as one of the following (a or b) (see Appendix D):
   a. CIS only;
   b. Ta/T1 high-grade disease with concomitant CIS;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Member is refractory to BCG treatment (see Appendix D); *Prior authorization may be required for BCG immunotherapy
2. For members who are not candidates for cystectomy, failure of intravesical chemotherapy, unless contraindicated or clinically significant adverse effects are experienced;

3. If request is for a dose increase, request meets one of the following (a or b): a. Dose does not exceed 75 mL (4 vials) of 3 x 1011 viral particles (vp)/mL; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 3 months (1 dose only)
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   CLINICAL POLICY Nadofaragene Firadenovec-vncg 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): 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. Non-Muscle Invasive Bladder Cancer (must meet all):
6. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Adstiladrin for a covered indication and has received this medication for at least 30 days;
7. Member is responding positively to therapy as evidenced by freedom from high-grade disease recurrence, as evaluated by cytology, cystoscopy, and/or biopsy;
8. Member has not yet received 4 total lifetime doses of Adstiladrin;
   4. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 75 mL (4 vials) of 3 x 1011 vp/mL every 3 months; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 3 months (1 dose only; total of four doses per lifetime) B. Other diagnoses/indications (must meet 1 or 2):

9. 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 Page 2 of 6

   CLINICAL POLICY Nadofaragene Firadenovec-vncg

10. 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 BCG: bacillus Calmette-Guerin CIS: carcinoma in-situ
    FDA: Food and Drug Administration NMIBC: non-muscle invasive bladder cancer Ta/T1: description of tumor growth
    Ta tumors are “papillary tumors”, T1 tumors have grown into the connective tissue of the bladder wall, but not into the muscle layer vp: viral particles 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.
    Drug Name Dosing Regimen Bacillus Calmette-Guerin vaccine (TICE BCG®) gemcitabine mitomycin 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. 1 to 8 × 108 CFU (a vial) intravesical instillation once per week for 6 weeks varies varies Dose Limit/ Maximum Dose 1 to 8 × 108 CFU per week varies varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to interferon alfa or any component of the product • Boxed warning(s): none Appendix D: General Information
    • Refractory or “BCG unresponsive” is defined as being at least one of the following:

11. Persistent or recurrent CIS alone or with recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy, defined as at least one of the following:
    a. At least 5 of 6 doses of an initial induction course plus at least 2 of 3 doses of maintenance therapy; b. At least 5 of 6 doses of an initial induction course plus at least 2 of 6 doses of the second induction course; Page 3 of 6

    CLINICAL POLICY Nadofaragene Firadenovec-vncg

12. Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy;
13. T1 high-grade disease at the first evaluation following an induction BCG course. V. Dosage and Administration
    Indication High grade, BCG unresponsive NMIBC
    Dosing Regimen Initial dose: 1 x 1011 vp/mL OR 3 x 1011 vp/mL Retreatment at months 4, 7, and 10 Maximum Dose 75 mL (4 vials) of 3 x 1011 vp/mL for a total of four doses VI. Product Availability
    Single-use vial: 3 x 1011 vp/mL; four single-dose vials per carton VII.