BRINEURA, Cerliponase Alfa Form

Cerliponase alfa (Brineura®) is a hydrolytic lysosomal N-terminal tripeptidyl peptidase. FDA Approved Indication(s) Brineura is indicated to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) 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 Brineura is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Late Infantile Neuronal Ceroid Lipofuscinosis Type 2 (must meet all):

1. Diagnosis of late infantile neuronal CLN2;
   2. Prescribed by or in consultation with a neurologist;
   3. Age ≥ 3 years;
   4. Confirmation of CLN2 with both of the following (a and b): a. TPP1 enzyme activity test demonstrating deficient TPP1 enzyme activity in leukocytes; b. Identification of 2 pathogenic mutations in trans in the TPP1/CLN2 gene;
2. Motor domain of the CLN2 Clinical Rating Scale score ≥ 1;
   6. At the time of request, member does not have ventriculoperitoneal shunts;
   7. Dose does not exceed 300 mg administered once every other week as an intraventricular infusion. 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): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: Page 1 of 6

   CLINICAL POLICY
   Cerliponase Alfa 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. Late Infantile Neuronal Ceroid Lipofuscinosis Type 2 (must meet all):
5. 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);
6. Member is responding positively to therapy as evidenced a score of ≥ 1 on the CLN2 Clinical Rating Scale;
7. If request is for a dose increase, new dose does not exceed 300 mg administered once every other week as an intraventricular infusion. Approval duration: 6 months
   B. Other diagnoses/indications (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.
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   CLINICAL POLICY
   Cerliponase Alfa 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 policy – 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 CLN2: ceroid lipofuscinosis type 2 FDA: Food and Drug Administration TPP1: tripeptidyl peptidase 1 Appendix B: Therapeutic Alternatives Not applicable Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
   o Acute, unresolved localized infection on or around the device insertion site (e.g. cellulitis or abscess); or suspected or confirmed CNS infection (e.g. cloudy CSF or positive CSF gram stain, or meningitis). o Acute intraventricular access device-related complications (e.g., leakage, device failure, or device-related infection) . o Patients with ventriculoperitoneal shunts. • Boxed warning(s): none reported Appendix D: Motor Domain of CLN2 Clinical Rating Scale • The motor domain of the CLN2 Clinical Rating Scale is scored as follow: walks normally = 3, intermittent falls, clumsiness, obvious instability = 2, no unaided walking or crawling only = 1, immobile, mostly bedridden = 0. • Decline is defined as having an unreversed (sustained) 2 category decline or an unreversed score of 0 in the motor domain of the CLN2 Clinical Rating Scale. V. Dosage and Administration
   Indication Dosing Regimen CLN2 300 mg administered once every other week as an intraventricular infusion followed by infusion of intraventricular electrolytes over approximately 4.5 hours Maximum Dose 300 mg every other week VI. Product Availability
   Injection: 150 mg/5 mL (30 mg/mL) solution, two single-dose vials per carton co-packaged with Intraventricular Electrolytes Injection 5 mL in a single-dose vial. VII.