ALDURAZYME, Laronidase Form

Laronidase (Aldurazyme®) is a hydrolytic lysosomal glycosaminoglycan-specific enzyme. FDA Approved Indication(s) Aldurazyme is indicated for adult and pediatric patients with Hurler and Hurler-Scheie forms of mucopolysaccharidosis I (MPS I) and for patients with the Scheie form who have moderate to severe symptoms.
Limitation(s) of use:
• The risks and benefits of treating mildly affected patients with the Scheie form have not been established.
• Aldurazyme has not been evaluated for effects on the central nervous system manifestations of the disorder.
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 Aldurazyme is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Mucopolysaccharidosis I: Hurler, Hurler-Scheie, and Scheie Forms (must meet all):

1. Diagnosis of MPS I: confirmed by one of the following (a or b): a. Enzyme assay demonstrating deficiency of alpha-L-iduronidase activity;
   b. DNA testing;
2. Member has one of the following (a or b): a. Hurler or Hurler-Scheie form of MPS I; b. Scheie form of MPS I with moderate to severe symptoms;

3. Age ≥ 6 months;

   4. Documentation of member’s current weight (in kg);
   5. Dose does not exceed 0.58 mg/kg per week (rounded up to the nearest whole vial). Approval duration:
      Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer Page 1 of 6

   CLINICAL POLICY Laronidase 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. Mucopolysaccharidosis I: Hurler, Hurler-Scheie, and Scheie Forms (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 improvement in the individual member’s MPS I disease manifestation profile (see Appendix D for examples);
8. Documentation of member’s current weight (in kg);
   4. If request is for a dose increase, new dose does not exceed 0.58 mg/kg per week (rounded up to the nearest whole vial).
      Approval duration:
      Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer 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 b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: Page 2 of 6

   CLINICAL POLICY Laronidase 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.
    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, CP.PMN.53 for Medicaid, or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key 6MWT: 6-minute walk test
    FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
    Not applicable
    FVC: forced vital capacity MPS: mucopolysaccharidosis Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported. • Boxed warning(s): risk of life-threatening anaphylactic reactions with Aldurazyme infusions. Appendix D: General Information • The presenting symptoms and clinical course of MPS I can vary from one individual to another. Some examples, however, of improvement in MPS I disease as a result of Aldurazyme therapy may include improvement in:
    o Percent predicted forced vital capacity (FVC); o 6-minute walk test (6MWT); o Joint stiffness, Carpal Tunnel Syndrome; o Upper airway infection recurrence; o Hepatomegaly, splenomegaly; o Growth deficiencies. In the clinical trials of Aldurazyme in patients ≥ 6 years of age, the mean increase in percent of predicted forced vital capacity (FVC) observed corresponded to a 10% relative improvement over the baseline FVC, which is considered by the American Thoracic Society to be a clinically significant change and not due to week-to-week variability.
    In the clinical trials of Aldurazyme in patients ≥ 6 years of age, patients treated with Aldurazyme demonstrated a 19.7 meter mean increase in the 6MWT after 26 weeks. • • Page 3 of 6

    CLINICAL POLICY Laronidase V. Dosage and Administration
    Indication MPS I Dosing Regimen Maximum Dose 0.58 mg/kg IV once weekly 0.58 mg/kg/week VI. Product Availability
    Vial: 2.9 mg/5 mL VII.