ERWINAZE, Asparaginase Erwinia Chrysanthemi Form

Asparaginase Erwinia chrysanthem (recombinant)-rywn (Rylaze®) is an asparagine specific enzyme. FDA Approved Indication(s) Rylaze is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of ALL and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase. Policy/Criteria Provider must submit documentation (including 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 Rylaze is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Lymphoblastic Leukemia (must meet all):

1. Diagnosis of ALL;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 1 month;
   4. Prescribed as a component of a multi-agent chemotherapeutic regimen;
   5. Member has developed hypersensitivity to an E. coli derived asparaginase product (Elspar® - off-market), pegaspargase (Oncaspar®), or calaspargase pegol-mknl (Asparlas®);

2. Request meets one of the following (a, b, or c): a. Dose does not exceed 25 mg/m2 every 48 hours; b. Dose does not exceed 25 mg/m2 on Monday and Wednesday and 50 mg/m2 on Friday; 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:
   Medicaid/HIM – 3 months Commercial – 6 months or duration of request, whichever is less Page 1 of 7

   CLINICAL POLICY Erwinia Asparaginase B. Lymphoblastic Lymphoma (must meet all):

3. Diagnosis of LBL;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 1 month;
   4. Prescribed as a component of a multi-agent chemotherapeutic regimen;
   5. Member has developed hypersensitivity to an E. coli derived asparaginase product (Elspar - off-market) or pegaspargase (Oncaspar);
4. Request meets one of the following (a, b, c): a. Dose does not exceed 25 mg/m2 every 48 hours; b. Dose does not exceed 25 mg/m2 on Monday and Wednesday and 50 mg/m2 on Friday; 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:
   Medicaid/HIM – 3 months Commercial – 6 months or duration of request, whichever is less C. T-Cell Lymphoma (off-label) (must meet all):
5. Diagnosis of extranodal NK/T-cell lymphoma;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Member has developed hypersensitivity to an E. coli derived asparaginase product (Elspar - off-market) or pegaspargase (Oncaspar);
6. Dose is within FDA maximum limit for any FDA-approved indication or 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:
   Medicaid/HIM – 3 months Commercial – 6 months or duration of request, whichever is less D. 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 Page 2 of 7

   CLINICAL POLICY Erwinia Asparaginase

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.
   II. Continued Therapy A. All Indications in Section I (must meet all):
9. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Rylaze for a covered indication and has received this medication for at least 30 days;
10. 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. Dose does not exceed 25 mg/m2 every 48 hours; b. Dose does not exceed 25 mg/m2 on Monday and Wednesday and 50 mg/m2 on Friday; 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:
       Medicaid/HIM – 6 months Commercial – 6 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
11. 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

12. 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 policy – Page 3 of 7

    CLINICAL POLICY Erwinia Asparaginase 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 ALL: acute lymphoblastic leukemia FDA: Food and Drug Administration LBL: lymphoblastic lymphoma Appendix B: Therapeutic Alternatives
    Not applicable
    Appendix C: Contraindications/Boxed Warnings • Contraindication(s): history of serious hypersensitivity reactions to Rylaze, including anaphylaxis, serious pancreatitis with prior L-asparaginase therapy, serious thrombosis with prior L-asparaginase therapy, serious hemorrhagic events with prior L-asparaginase therapy. • Boxed warning(s): None reported. V. Dosage and Administration
    Indication Dosing Regimen ALL, LBL When replacing a long-acting asparginase product the recommended dose is: • 25 mg/m2 IM every 48 hours OR • 25 mg/m2 IM on Monday morning and Wednesday morning, and 50 mg/m2 IM on Friday afternoon Maximum Dose 50 mg/m2/dose VI. Product Availability
    Single-dose vial for injection: 10 mg/0.5 ml VII.