Lumasiran (Oxlumo) Form

Lumasiran (Oxlumo®) is an RNAi therapeutic targeting glycolate oxidase (GO). FDA Approved Indication(s) Oxlumo is indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary and plasma oxalate levels in pediatric and adult patients. 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 Oxlumo is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Primary Hyperoxaluria Type 1 (must meet all):

1. Diagnosis of PH type 1 confirmed by one of the following (a or b): a. Genetic testing confirming presence of mutations in the AGXT gene; b. Liver biopsy confirming AGT enzyme deficiency;
2. Prescribed by or in consultation with an endocrinologist, hepatologist, or nephrologist;
3. Documentation of one of the following (a, b, or c): a. Urinary oxalate (UOx) excretion > 0.70 mmol/1.73 m2/24 h, confirmed on repeat testing; b. Spot urinary oxalate-to-creatinine (UOx:Cr) molar ratio greater than normal for age (see Appendix D for reference ranges), confirmed on repeat testing; c. Plasma oxalate (POx) levels ≥ 20 µmol/L;
4. Failure to achieve normalization of UOx excretion levels after at least three months of pyridoxine (vitamin B6) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
   *Normal UOx excretion is < 0.50 mmol (< 45 mg)/1.73 m2/day, or see Appendix D for reference ranges for age-specific spot UOx:Cr molar ratios.

5. Member has not had a liver transplant;

   6. If on dialysis, member is on hemodialysis only for at least 4 weeks;
   7. Documentation of member’s current body weight (in kg);
   8. Dose does not exceed any of the following, based on body weight (a, b, or c): a. < 10 kg: 6 mg/kg per month for 3 doses followed by 3 mg/kg per month; Page 1 of 7

   CLINICAL POLICY Lumasiran b. 10 kg to < 20 kg: 6 mg/kg per month for 3 doses followed by 6 mg/kg every 3 months; c. ≥ 20 kg: 3 mg/kg per month for 3 doses followed by 3 mg/kg every 3 months. 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):

6. 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
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: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Primary Hyperoxaluria Type 1 (must meet all):
   
   1. 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);
8. Member is responding positively to therapy as evidenced by one of the following (a or b): a. Decrease from baseline in UOx excretion of > 30%; b. Decrease from baseline in UOx excretion or plasma oxalate levels or improvement in spot UOx:Cr molar ratio, along with improvement in PH1 symptoms (e.g., nephrolithiasis, nephrocalcinosis, kidney function, ischemic skin ulcers, metabolic bone disease, refractory anemia, cardiomyopathy, abnormalities in cardiac conduction);

9. Member has not had a liver transplant;

   4. Documentation of member’s current body weight (in kg);
   5. If request is for a dose increase, new dose does not exceed any of the following, based on body weight (a, b, or c): a. < 10 kg: 3 mg/kg per month; Page 2 of 7

   CLINICAL POLICY Lumasiran b. 10 kg to < 20 kg: 6 mg/kg every 3 months; c. ≥ 20 kg: 3 mg/kg every 3 months. Approval duration:
   Medicaid/HIM – 12 months Commercial – 6 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

10. 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

11. 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 eGFR: estimated glomerular filtration rate
    FDA: Food and Drug Administration GO: glycolate oxidase PH1: primary hyperoxaluria type 1 POx: plasma oxalate RNAi: RNA interference UOx: urinary oxalate UOx:Cr: urinary oxalate-to-creatinine 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.
    Dosing Regimen Drug Name Dose Limit/ Maximum Dose 20 mg/kg/day pyridoxine 5-20 mg/kg PO QD Page 3 of 7

    CLINICAL POLICY Lumasiran 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. Appendix C: Contraindications/Boxed Warnings None reported
    Appendix D: Spot UOx/Cr Molar Ratio Reference Ranges in Spot Urine Samples Age 0-6 months 7-24 months 2-5 years 5-14 years

    16 years Normal Values < 325-360 mmol/mol (< 253-282 mg/g) < 132-174 mmol/mol (< 103-136 mg/g) < 98-101 mmol/mol (< 76-79 mg/g) < 70-82 mmol/mol (< 55-64 mg/g) < 40 mmol/mol (< 32 mg/g) V. Dosage and Administration Indication PH1 Dosing Regimen If weight is: • < 10 kg: 6 mg/kg/month SC for 3 doses followed by 3 mg/kg/month SC; • 10 kg to < 20 kg: 6 mg/kg/month SC for 3 doses followed by 6 mg/kg SC
    every 3 months; • ≥ 20 kg: 3 mg/kg/month SC for 3 doses followed by 3 mg/kg SC every 3 months Maximum Dose If weight is: • < 10 kg: 3 mg/kg/month; • 10 kg to < 20 kg: 6 mg/kg every 3 months; • ≥ 20 kg: 3 mg/kg every 3 months VI. Product Availability Solution in single-dose vial: 94.5 mg/0.5 mL VII.