Sutimlimab-jome (Enjaymo) Form

Sutimlimab-jome (Enjaymo™) is a classical complement inhibitor. FDA Approved Indication(s)
Enjaymo is indicated for the treatment of hemolysis in adults with cold agglutinin disease (CAD). 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 Enjaymo is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Cold Agglutinin Disease (must meet all):

1. Diagnosis of primary CAD;
   2. Prescribed by or in consultation with a hematologist or oncologist;
   3. Age ≥ 18 years;
   4. Secondary CAD has been ruled out (i.e., cold agglutinin syndrome secondary to infection, rheumatologic disease, or active hematologic malignancy);
2. Member meets all of the following (a, b, c, and d):
   a. Active hemolysis as evidenced by elevated total bilirubin; b. Polyspecific direct antiglobulin test (DAT) (i.e., Coombs test) is positive;
   c. Monospecific DAT shows both of the following (i and ii): i. C3d DAT: strongly positive;
   ii. IgG DAT: negative or weakly positive; d. Cold agglutinin titer ≥ 64 at 4 degrees Celsius;

3. Hemoglobin ≤ 10 g/dL;

   7. Enjaymo is not prescribed concurrently with rituximab or rituximab-based regimens (i.e., rituximab with bendamustine or fludarabine);
   8. Dose does not exceed one of the following (a or b): a. For body weight 39 kg to < 75 kg: 6,500 mg (6 vials) on Day 0, Day 7, then every 2 weeks thereafter; b. For body weight ≥ 75 kg: 7,500 m (7 vials) on Day 0, Day 7, then every 2 weeks thereafter . Approval duration: 6 months
      Page 1 of 6

   CLINICAL POLICY Sutimlimab-jome 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. Cold Agglutinin Disease (must meet all):
6. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
7. Member is responding positively to therapy as evidenced by one of the following since initiation of Enjaymo therapy (a or b): a. Increase in hemoglobin ≥ 1.5 g/dL or hemoglobin level ≥ 12 g/dL; b. Transfusion free or decreased number of transfusions/blood units;
8. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. For body weight 39 kg to < 75 kg: 6,500 mg (6 vials) every 2 weeks; b. For body weight ≥ 75 kg: 7,500 mg (7 vials) every 2 weeks. Approval duration: 12 months 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 Page 2 of 6

   CLINICAL POLICY Sutimlimab-jome 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

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 Approval duration: Duration of request or 6 months (whichever is less) 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 CAD: cold agglutinin disease DAT: direct antiglobulin test FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
    Not applicable Appendix C: Contraindications/Boxed Warnings
    • Contraindication(s): known hypersensitivity to sutimlimab-jome or any inactive ingredients • Boxed warning(s): none reported Appendix D: Cold Agglutinins • During passage through acral parts of the body, cooling of the blood allows cold agglutinins (CA) to bind to erythrocytes and cause agglutination.
    • The antigen-IgM complex binds complement protein 1q (C1q) on the cell surface and initiates the classical complement pathway.
    • C1 esterase activates C2 and C4, generating C3 convertase which results in the cleavage of C3 to C3a and C3b.
    • Upon warming to 37°C in the central circulation, the CA detach from the cells, allowing agglutinated erythrocytes to separate, while C3b remains bound.
    • C3b-opsonized cells are prone to phagocytosis by the mononuclear phagocytic system, mainly in the liver, a process known as extravascular hemolysis.
    • On the surface of the surviving erythrocytes, C3b is cleaved, leaving high numbers of C3d molecules that can be detected by the DAT. ___ Page 3 of 6

    CLINICAL POLICY Sutimlimab-jome Berentsen S. How I manage patients with cold agglutinin disease. British Journal of Haematology. 2018;181:320–330. V. Dosage and Administration Indication Dosing Regimen CAD Weight-based dose IV weekly for 2 weeks then every 2 weeks thereafter: • 39 kg to < 75 kg: 6,500 mg (6 vials) • ≥ 75 kg: 7,500 mg (7 vials) Maximum Dose 39 kg to < 75 kg: 6,500 mg/dose ≥ 75 kg: 7,500 mg/dose Must be administered at the recommended dosage regimen time points or within 2 days of these time points VI. Product Availability Solution for injection in single-dose vial: 1,100 mg/22 mL (50 mg/mL)
    VII.