ONIVYDE, Irinotecan HCl Liposome Form

Irinotecan liposome injection (Onivyde®) is a topoisomerase inhibitor. FDA Approved Indication(s) Onivyde is indicated: • In combination with oxaliplatin, fluorouracil and leucovorin, for the first-line treatment of patients with metastatic pancreatic adenocarcinoma; In combination with fluorouracil and leucovorin, for the treatment of patients with metastatic pancreatic adenocarcinoma after disease progression following gemcitabine-based therapy. • Limitation(s) of use: Onivyde is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas. 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 Onivyde is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Pancreatic Adenocarcinoma (must meet all):

1. Diagnosis of locally advanced, metastatic, or recurrent pancreatic adenocarcinoma;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed in one of the following ways (a or b): a. In combination with oxaliplatin, fluorouracil, and leucovorin (i.e., as a component of the NALIRIFOX regimen; see Appendix D) as first-line therapy; b. In combination with fluorouracil and leucovorin for disease progression following gemcitabine-based therapy, or fluoropyrimidine-based therapy without prior irinotecan;

2. Request meets one of the following (a, b, or c):* a. Dose does not exceed 50 mg/m2 every 2 weeks when used as a component of the NALIRIFOX regimen; b. Dose does not exceed 70 mg/m2 every 2 weeks when prescribed in combination with flurouracil and leucovorin only; Page 1 of 6

   CLINICAL POLICY
   Irinotecan Liposome c. 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: 6 months
   B. Other diagnoses/indications (must meet 1 or 2):

3. 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: 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or
   2. 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: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. Pancreatic Adenocarcinoma (must meet all):
4. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Onivyde for a covered indication and has received this medication for at least 30 days;
5. Member is responding positively to therapy;
   3. If request is for a dose increase, request meets one of the following (a, b, or c): a. New dose does not exceed 50 mg/m2 every 2 weeks as a component of the NALIRIFOX regimen; b. New dose does not exceed 70 mg/m2 every 2 weeks in combination with fluorouracil and leucovorin only; c. 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: 12 months B. Other diagnoses/indications (must meet 1 or 2):

6. 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: 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or Page 2 of 6

   CLINICAL POLICY
   Irinotecan Liposome

7. 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: 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.PMN.53 for Medicaid and HIM.PA.154 for health insurance marketplace, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration NCCN: National Comprehensive Cancer Network 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 Dose Limit/ Maximum Dose Varies Examples of gemcitabine-containing regimens: gemcitabine alone or with any of the following: capecitabine, fluorouracil and leucovorin, albumin-bound paclitaxel and/or cisplatin, erlotinib, docetaxel and capecitabine
   Examples of fluoropyrimidine-based regimens: fluorouracil with any of the following: leucovorin, irinotecan/ liposomal irinotecan, and oxaliplatin
   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. Varies Varies Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): severe hypersensitivity reaction to Onivyde or irinotecan HCl • Boxed warning(s): severe neutropenia and severe diarrhea; do not administer in patients with bowel obstruction Appendix D: NALIRIFOX
   • NALIRIFOX regimen contains fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin Page 3 of 6

   CLINICAL POLICY
   Irinotecan Liposome V. Dosage and Administration
   Indication Dosing Regimen Pancreatic adenocarcinoma • 50 mg/m2 IV every 2 weeks when used prior to leucovorin, fluorouracil, and oxaliplatin • 70 mg/m2 IV every 2 weeks when used prior to • leucovorin and fluorouracil only If homozygous for UGT1A1*28 allele: 50 mg/m2 IV every 2 weeks. Increase the dose to 70 mg/m2 as tolerated in subsequent cycles. VI. Product Availability
   Single-dose vial: 43 mg/10 mL Maximum Dose 70 mg/m2 every 2 weeks VII.