Elivaldogene Autotemcel Form

Elivaldogene autotemcel (Skysona®) is a genetically modified autologous CD34+ cell enriched population that contains hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding ABCD1 complementary deoxyribonucleic acid (cDNA) for human adrenoleukodystrophy protein. FDA Approved Indication(s)
Skysona is indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD). Early, active CALD refers to asymptomatic or mildly symptomatic (neurologic function score, NFS ≤ 1) boys who have gadolinium enhancement on brain magnetic resonance imaging (MRI) and Loes scores of 0.5-9. This indication is approved under accelerated approval based on 24-month Major Functional Disability (MFD)-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Limitation(s) of use: • Skysona does not treat or prevent adrenal insufficiency. • An immune response to Skysona may cause rapid loss of efficacy of Skysona in patients with full deletions of the ABCD1 gene. • Skysona has not been studied in CALD secondary to head trauma. • Given the risk of hematologic malignancy with Skysona, and unclear long-term durability of Skysona and human adrenoleukodystrophy protein (ALDP) expression, careful consideration should be given to the timing of treatment for each boy and treatment of boys with isolated pyramidal tract disease as clinical manifestations do not usually occur until adulthood. 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.
All requests reviewed under this policy require medical director review.
It is the policy of health plans affiliated with Centene Corporation® that Skysona is medically necessary when the following criteria are met:
I. Initial Approval Criteria
*Only for initial treatment dose; subsequent doses will not be covered. Page 1 of 7

CLINICAL POLICY Elivaldogene Autotemcel A. Cerebral Adrenoleukodystrophy (must meet all):

1. Diagnosis of adrenoleukodystrophy with both of the following (a and b): a. Genetic confirmation of ABCD1 mutation; b. Elevated levels of very long chain fatty acids (VLCFA) (see Appendix E);
2. Prescribed by or in consultation with both (a and b): a. Neurologist;
   b. Transplant specialist;
   
   3. Member is a biologic male;
   4. Age between 4 and 17 years;
   5. Early, active CNS disease established by brain MRI demonstrating both of the following (a and b): a. Loes score ≥ 0.5 and ≤ 9 on the 34-point scale (see Appendix D); b. Gadolinium enhancement of demyelinating lesions on MRI;
3. Member has an NFS ≤ 1 (see Appendix D);
   7. One of the following (a or b): a. Member has no available HLA (human leukocyte antigen)-matched (i.e., full HLA-matching of all evaluated alleles) donor; b. Member has an available HLA-matched donor, and both of the following (i and ii): i. Provider submits medical rationale that allogeneic hematopoietic stem cell transplantation (HSCT) is not feasible (e.g., donor unable to undergo donation procedure because of medical impairments);
      ii. Member understands the risks and benefits of alternative therapeutic options such as allogeneic HSCT;
4. Transplant specialist attestation that member is clinically stable and eligible to undergo myeloablative conditioning and HSCT;
5. Member has not received prior allogeneic HSCT or gene therapy; 10. For members with CALD and isolated pyramidal tract disease: Hematology specialist attestation of both of the following (a and b): a. Member understands the potential increased risk of malignancy associated with Skysona treatment; b. Applicable hematology assessments have been performed (see Appendix F for examples);
6. Member is not positive for the presence of HIV type 1 or 2; 12. Dose contains a minimum of 5 x 106 CD34+ cells/kg.
   Approval duration: 3 months (one time infusion per lifetime)
   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 Page 2 of 7

   CLINICAL POLICY Elivaldogene Autotemcel 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. II. Continued Therapy A. Cerebral Adrenoleukodystrophy
9. Continued therapy will not be authorized as Skysona is indicated to be dosed one time only. Approval duration: Not applicable 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 2 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 ABCD1: adenosine triphosphate binding cassette, sub family D, member 1
    ALDP: adrenoleukodystrophy protein CALD: cerebral adrenoleukodystrophy cDNA: complementary deoxyribonucleic acid FDA: Food and Drug Administration HLA: human leukocyte antigen Page 3 of 7

    CLINICAL POLICY Elivaldogene Autotemcel HSCT: hematopoietic stem cell transplantation MFD: major functional disability MRI: magnetic resonance imaging NFS: neurologic function score VLCFA: very long chain fatty acids Appendix B: Therapeutic Alternatives
    Not applicable
    Appendix C: Contraindications/Boxed Warnings
    • Contraindication(s): none • Boxed warning(s): hematologic malignancy Appendix D: General Information
    • The Loes score is a rating of the severity of abnormalities in the brain found on MRI. It ranges from 0 to 34, based on a point system derived from the location and extent of disease and the presence of atrophy in the brain, either localized to specific points or generally throughout the brain. A score of 0 indicates a normal MRI, and higher scores indicate increased severity of cerebral lesions.
    • The CALD NFS is a 25-point score used to evaluate the severity of gross neurologic dysfunction across 15 symptoms in six categories. An NFS of 0 indicates that there is no observed impairment in the neurologic functions that are assessed on the 25-point scale, and higher scores correspond to increasing severity of functional deficits.
    Appendix E: VLCFA Lab Reference Ranges VLCFAs C26:0 µmol/L C24:0/C22:0 ratio C26:0/C22:0 ratio VLCFA lab reference ranges may vary
    Normal Levels 0.67 +/- 0.13 0.86 +/- 0.13 0.01 +/- 0.003 Males with ALD 2.94 +/- 0.87 1.52 +/- 0.21 0.05 +/- 0.02 Appendix F: Baseline Hematologic Assessments for CALD with isolated pyramidal tract disease • Complete blood count with differential
    • Hematopathology review of peripheral blood smear
    • Hematopathology review of bone marrow biopsy (core and aspirate) with flow cytometry, conventional karyotyping, and next generation sequencing (NGS) with a molecular panel appropriate for age and including coverage for gene mutations expected in myeloid and lymphoid malignancies • Testing for germline mutations that are associated with hematologic malignancy V. Dosage and Administration
    Indication Dosing Regimen CALD Minimum recommended dose: 5.0 × 106 CD34+ cells/kg None Maximum Dose VI. Product Availability
    Single-dose cell suspension: up to two infusion bags of genetically modified autologous cells enriched for CD34+ cells labeled for the specific recipient
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    CLINICAL POLICY Elivaldogene Autotemcel VII.