JADENU, Deferasirox EXJADE, Deferasirox Form

Deferasirox (Exjade®, Jadenu®) is an iron chelator. FDA Approved Indication(s) Exjade and Jadenu are indicated for the treatment of: • Chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older.
• Chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes and with a liver iron concentration (LIC) of at least 5 milligrams of iron per gram of liver dry weight (mg Fe/g dw) and a serum ferritin greater than 300 mcg/L.
Limitation(s) of use: The safety and efficacy of Exjade/Jadenu when administered with other iron chelation therapy have not been established. 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 Exjade and Jadenu are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Iron Overload due to Blood Transfusions (must meet all):

1. Diagnosis of chronic iron overload due to blood transfusions;
2. Age ≥ 2 years;
3. Member must use generic deferasirox, unless contraindicated or clinically significant adverse effects are experienced;
   4. Transfusion history of ≥ 100 mL/kg of packed red blood cells (e.g., ≥ 20 units of packed red blood cells for a 40 kg person) and a serum ferritin level > 1,000 mcg/L;
   5. At the time of the request, member has none of the following contraindications: a. Glomerular filtration rate (GFR) < 40 mL/min/1.73 m2; b. Platelet count < 50 x 109/L; c. Severe hepatic impairment (Child-Pugh C);
   6. Therapy does not include concurrent use of other iron chelators;

4. Dose does not exceed the following (a or b):
   a. Exjade: 40 mg/kg per day (see Appendix D for dose rounding guidelines); Page 1 of 8

   CLINICAL POLICY Deferasirox b. Jadenu: 28 mg/kg per day (see Appendix D for dose rounding guidelines). Approval duration: 6 months B. Chronic Iron Overload due to Non-Transfusion-Dependent Thalassemia Syndromes (must meet all):

5. Diagnosis of chronic iron overload due to NTDT;
6. Age ≥ 10 years;
7. Member must use generic deferasirox, unless contraindicated or clinically significant adverse effects are experienced;
   4. Documentation of serum ferritin level > 300 mcg/L and LIC ≥ 5 mg Fe/g dw;
8. Therapy does not include concurrent use of other iron chelators;

9. At the time of the request, member has none of the following contraindications: a. GFR < 40 mL/min/1.73 m2; b. Platelet count < 50 x 109/L; c. Severe hepatic impairment (Child-Pugh C);

   7. Dose does not exceed the following (a or b): a. Exjade: 20 mg/kg per day (see Appendix D for dose rounding guidelines); b. Jadenu: 14 mg/kg per day (see Appendix D for dose rounding guidelines). Approval duration: 6 months C. Other diagnoses/indications (must meet 1 or 2):
   8. 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
   9. 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. Chronic Iron Overload due to Blood Transfusions (must meet all):
   10. 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); Page 2 of 8

   CLINICAL POLICY Deferasirox

   2. Current documentation (within the past 30 days) shows serum ferritin level ≥ 500 mcg/L;
   3. Therapy does not include concurrent use of other iron chelators;
10. If request is for a dose increase, new dose does not exceed the following (a or b):
    a. Exjade: 40 mg/kg per day (see Appendix D for dose rounding guidelines); b. Jadenu: 28 mg/kg per day (see Appendix D for dose rounding guidelines). Approval duration: 12 months B. Chronic Iron Overload due to Non-Transfusion-Dependent Thalassemia Syndromes (must meet all):
11. 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);
    2. Current documentation (serum ferritin within past 30 days; LIC within past 90 days) shows one of the following (a or b): a. If member has received < 6 months of Exjade/Jadenu, serum ferritin level ≥ 300 mcg/L or LIC ≥ 3 mg Fe/g dw; b. If member has received ≥ 6 months of Exjade/Jadenu, LIC ≥ 3 mg Fe/g dw;
    3. Therapy does not include concurrent use of other iron chelators;

12. If request is for a dose increase, new dose does not exceed the following (a or b):
    a. Exjade: 20 mg/kg per day (see Appendix D for dose rounding guidelines); b. Jadenu: 14 mg/kg per day (see Appendix D for dose rounding guidelines). Approval duration: 12 months C. Other diagnoses/indications (must meet 1 or 2):

    1. 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
    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: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
       Page 3 of 8

    CLINICAL POLICY Deferasirox 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;
    B. Parkinson’s disease. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration Fe/g dw: iron in milligrams per gram dry weight Appendix B: Therapeutic Alternatives
    Not applicable GFR: glomerular filtration rate LIC: liver iron concentration NTDT: non-transfusion-dependent thalassemia Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Estimated GFR < 40 mL/min/1.73 m2 o Poor performance status o High-risk myelodysplastic syndromes o Advanced malignancies o Platelet count < 50 x 109/L o Known hypersensitivity to deferasirox or any component of Exjade or Jadenu • Boxed warning(s): renal failure, hepatic failure, and gastrointestinal hemorrhage Tablet for Oral Solution Quantity Recommendation 125 mg tablet
    250 mg tablet
    125 mg tablet and 250 mg tablet 500 mg tablet 125 mg tablet and 500 mg tablet 250 mg tablet and 500 mg tablet 125 mg tablet, 250 mg tablet and 500 mg tablet 2 x 500 mg tablets 125 mg tablet and 2 x 500 mg tablets
    250 mg tablet and 2 x 500 mg tablets
    125 mg tablet, 250 mg tablet and 2 x 500 mg tablets
    3 x 500 mg tablets Appendix D: Dose Rounding Guidelines* Weight-based Dose Range ≤ 131.24 mg
    131.25 mg – 262.49 mg 262.5 mg – 392.99 mg
    393 mg – 524.99 mg 525 mg – 655.99 mg
    656 mg – 787.49 mg
    787.5 mg – 917.99 mg
    918 mg – 1,049.99 mg 1,050 mg – 1,180.99 mg
    1,181 mg – 1,312.49 mg
    1,312.5 mg – 1,442.99 mg
    1,443 mg – 1,574.99 mg
    Weight-based Dose Range Oral Granules (sachets) Quantity Recommendation ≤ 94.49 mg
    94.5 mg – 188.99 mg 189 mg – 283.49 mg
    283.5 mg – 377.99 mg 90 mg sachet
    180 mg sachet 90 mg sachet and 180 mg sachet 360 mg sachet Page 4 of 8

    CLINICAL POLICY Deferasirox Weight-based Dose Range Oral Granules (sachets) Quantity Recommendation 378 mg – 472.49 mg
    472.5 mg – 566.99 mg
    567 mg – 661.49 mg
    661.5 mg – 755.99 mg 756 mg – 850.49 mg
    850.5 mg – 944.99 mg
    945 mg – 1,039.49 mg
    1,039.5 mg – 1,133.99 mg
    *This is part of a dose rounding guideline on select drug classes as part of an initiative conducted on a larger scale with multiple references and prescriber feedback.
    90 mg sachet and 360 mg sachet 180 mg sachet and 360 mg sachet 90 mg sachet, 180 mg sachet and 360 mg sachet 2 x 360 mg sachets 90 mg sachet and 2 x 360 mg sachets 180 mg sachet and 2 x 360 mg sachets 90 mg sachet, 180 mg sachet and 2 x 360 mg sachets 3 x 360 mg sachets Appendix E: General Information
    • In FAIRPARK-II, deferiprone, an iron chelator, was associated with worse scores in measures of parkinsonism compared to placebo over a 36-week period in participants with newly diagnosed Parkinson’s disease who had never received levodopa.
    V. Dosage and Administration
    Drug Name Deferasirox (Exjade) Deferasirox (Jadenu) Indication Transfusional iron overload NTDT syndromes Transfusional iron overload NTDT syndromes Dosing Regimen 20 mg/kg body weight (calculate dose to the nearest whole tablet) PO QD 10 mg/kg body weight (calculate dose to the nearest whole tablet) PO QD 14 mg/kg body weight (calculated to nearest whole tablet/sachet) PO QD 7 mg/kg body weight (calculated to nearest whole tablet/sachet) PO QD Maximum Dose 40 mg/kg/day 20 mg/kg/day 28 mg/kg/day
    14 mg/kg/day VI. Product Availability
    Drug Deferasirox (Exjade) Deferasirox (Jadenu) Availability
    Tablets for oral suspension: 125 mg, 250 mg, 500 mg Tablets/sprinkle (sachets): 90 mg, 180 mg, 360 mg VII. References

13. Exjade Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; July 2020. Available at: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/exjade.pdf. Accessed May 9, 2022.

    2. Jadenu Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; July 2020. Available at: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/jadenu.pdf. Accessed May 9, 2022.
    3. Musallam KM, Angastiniotis M, Eleftheriou A, Porter JB. Cross-talk between available guidelines for the management of patients with beta-thalassemia major. Acta Haematol. 2013; 130: 64-73. DOI: 10.1159/000345734. Page 5 of 8

    CLINICAL POLICY Deferasirox

    4. Hoffbrand AV, Taher A, Cappellini MD. How I treat tranfusional iron overload. Blood. November 1, 2012; 120(18): 3657-3669.
    5. Taher AT, Viprakasit V, Musallam KM, Cappellini MD. Treating iron overload in patients with non-transfusion-dependent thalassemia: Critical Review. Am J Hematol. 2013; 88: 409-
14. DOI: 10.1002/ajh.23405.
    6. Taher A, Musallam K, Cappellini MD. Guidelines for the management of non-transfusion dependent thalassaemia (NTDT) 2nd edition. Thalassaemia International Federation. 2018. TIF publication No. 22.
    7. Cappellini MD, Farmakis D, Porter J, et al. 2021 Guidelines for the management of transfusion dependent thalassemia (TDT) 4th edition. Thalassaemia International Federation.
15. Available at: https://thalassaemia.org.cy/publications/tif-publications/guidelines-for- the-management-of-transfusion-dependent-thalassaemia-4th-edition-2021/. Accessed May 4,
16. 8. Devos D, Labreuche J, Rascol O, et al. Trial of deferiprone in Parkinson’s disease. N Engl J Med 2022; 387:2045-2055.
       Reviews, Revisions, and Approvals Date 03.05.20 05.14.19 3Q 2019 annual review: contraindications caveat added to required Jadenu trial; the following contraindications are added: platelets, GFR; Child Pugh C restriction is removed; added requirement that member does not have severe hepatic impairment; references reviewed and updated.