KANUMA, Sebelipase Alfa Form

Sebelipase alfa (Kanuma®) is a hydrolytic lysosomal cholesteryl ester and triacylglycerol- specific enzyme. FDA Approved Indication(s) Kanuma is indicated for the treatment of patients with a diagnosis of lysosomal acid lipase (LAL) deficiency. 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 Kanuma is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Lysosomal Acid Lipase Deficiency (must meet all):

1. Diagnosis of LAL deficiency confirmed by one of the following (a or b): a. Enzyme assay demonstrating a deficiency of LAL activity;
   b. Lipase A - lysosomal acid type (LIPA) gene mutation;
2. Age ≥ 1 month;
   3. Documentation of member’s current weight (in kg);
   4. Request meets one of the following (a or b): a. Dose does not exceed 3 mg/kg every other week; b. For members with rapidly progressive disease presenting within the first 6 months of life: Dose does not exceed any of the following (i or ii): i. 3 mg/kg per week; ii. 5 mg/kg per week, upon documentation of suboptimal clinical response to 3 mg/kg per week.Suboptimal clinical response is defined as any of the following: poor growth, deteriorating biochemical markers, or persistent or worsening organomegaly.
      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): Page 1 of 7

   CLINICAL POLICY
   Sebelipase Alfa 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

4. 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. Lysosomal Acid Lipase Deficiency (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);
5. Member is responding positively to therapy as evidenced by documentation of clinical response which may include, but is not limited to: a. For members with rapidly progressive disease presenting within first 6 months of life: continued survival;
   b. For all other members: decrease in low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein cholesterol (non-HDL-c), or triglycerides; increase in HDL-c; normalization of alanine aminotransferase (ALT) or aspartate aminotransferase (AST); reduction in hepatic fat content, steatosis, or liver volume;

6. Documentation of member’s current weight (in kg);

   4. If request is for a dose increase, new dose does not exceed any of the following (a or b): a. 3 mg/kg every other week; b. For members with rapidly progressive disease presenting within the first 6 months of life: Dose does not exceed any of the following (i or ii): i. 3 mg/kg per week; ii. 5 mg/kg per week, upon documentation of suboptimal clinical response to 3 mg/kg per week.Suboptimal clinical response is defined as any of the following: poor growth, deteriorating biochemical markers, or persistent or worsening organomegaly.
      Approval duration: 12 months Page 2 of 7

   CLINICAL POLICY
   Sebelipase Alfa B. 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

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.
   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 ALT: alanine aminotransferase AST: aspartate aminotransferase FDA: Food and Drug Administration HDL-c: non-high-density lipoprotein cholesterol Appendix B: Therapeutic Alternatives Not applicable LAL: lysosomal acid lipase LDL-c: low-density lipoprotein cholesterol LIPA: lipase A – lysosomal acid type Appendix C: Contraindications/Boxed Warnings None reported Appendix D: Measures of Therapeutic Response • LAL normally causes the breakdown of lipid particles, including LDL-c. A lack of LAL results in accumulation of cholesteryl esters and triglycerides. Therefore, LDL-c, non- HDL-c, triglycerides, and HDL-c are clinical parameters that can indicate therapeutic response to Kanuma. In clinical trials, there were initial increases in LDL-c and triglycerides within the first 2-4 weeks of treatment; however, this was followed by a decrease to below pre-treatment values within 8 weeks of treatment. Page 3 of 7

   CLINICAL POLICY
   Sebelipase Alfa • In addition, the lipid accumulation seen in LAL deficiency can occur in multiple organs, including the liver. This results in increased liver fat content and progression of liver disease, including fibrosis and cirrhosis. In clinical trials, patients receiving Kanuma had normalization of ALT and AST levels, reduction in hepatic fat content and steatosis (defined as the absolute decrease of ≥ 5% from baseline in assessment of hepatic fat content), and decrease in baseline liver volume when compared to patients receiving placebo. As such, improvement in these areas may also indicate positive response to Kanuma. ___ Not statistically significant V. Dosage and Administration
   Indication LAL deficiency: rapidly progressive disease presenting within first 6 months of life LAL deficiency Dosing Regimen 1 mg/kg IV once weekly
   Maximum Dose 5 mg/kg/week For patients with a suboptimal clinical response, increase the dosage to 3 mg/kg once weekly. For patients with continued suboptimal clinical response, further increase the dosage to 5 mg/kg once weekly. Suboptimal clinical response is defined as any of the following: poor growth, deteriorating biochemical markers, or persistent or worsening organomegaly.
   1 mg/kg IV every other week For patients with a suboptimal clinical response, increase the dosage to 3 mg/kg once every other week.* **Suboptimal clinical response is defined as any of the following: poor growth, deteriorating biochemical markers [e.g., alanine aminotransferase (ALT), aspartate aminotransferase (AST)], and/or parameters of lipid metabolism [e.g., low-density lipoprotein cholesterol (LDL- c), triglycerides (TG)]. 3 mg/kg every other week VI. Product Availability
   Single-use vial: 20 mg/10 mL VII.