Coverage Policy Manual
Policy #: 2023007
Category: Pharmacy
Initiated: February 2023
Last Review: January 2025
  Elivaldogene autotemcel (e.g., Skysona)
Description:
Elivaldogene autotemcel is an autologous gene therapy indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD).
 
Adrenoleukodystrophy (ALD) is a rare X-linked, metabolic disorder caused by a mutation in the ABCD1 gene which causes the buildup of very long chain fatty acids (VLCFAs) in the brain. CALD is the most common, most severe, and most neurodegenerative form of this condition. Since it is an X-linked disorder, it is more prevalent in males, particularly young males. Nearly half of individuals who do not receive treatment die within five years of symptom onset. Allogeneic hematopoietic stem cell transplant (allo-HSCT) is the treatment of choice for children with CALD. Allo-HSCT is associated with serious potential complications and mortality that increase in individuals without a matched sibling donor. More than 70% of individuals diagnosed with CALD do not have a matched sibling donor (Bluebird bio).
 
Elivaldogene autotemcel adds functional copies of the ABCD1 cDNA into individuals’ hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with Lenti-D LVV. After elivaldogene autotemcel infusion, transduced CD34+ HSCs engraft in the bone marrow and differentiate into various cell types, including monocytes (CD14+) capable of producing functional adrenoleukodystrophy protein (ALDP). Functional ALDP can then participate in the local degradation of VLCFAs, which is believed to slow or possibly prevent further inflammation and demyelination (FDA, 2022).
 
Regulatory Status
 
Elivaldogene autotemcel (e.g., Skysona) was approved under accelerated approval by the U.S. Food and Drug Administration (FDA) on September 16, 2022, for the treatment of cerebral adrenoleukodystrophy.
 
Limitations of Use (FDA, 2022)
 
    • SKYSONA does not treat or prevent adrenal insufficiency.  
    • An immune response to SKYSONA may cause rapid loss of efficacy of SKYSONA in individuals with full deletions of the human adenosine triphosphate binding cassette, sub family D, member 1 (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.  
 
Coding
 
There is no specific code at this time for elivaldogene autotemcel. Would expect to see this medication billed with:
 
J3590 – Unclassified Biologics
Policy/
Coverage:
Prior Approval is required for elivaldogene autotemcel (e.g., Skysona).
 
The initial use of this drug requires documentation of direct physician involvement (MD/DO) in the ordering and evaluation, as well as signature, in the medical records submitted for prior approval. Concurrent review will require continued evidence of appropriate physician involvement.
 
Approval timeframes may differ for members/participants of Self-Insured plans.
 
Effective January 2025
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
STANDARD REVIEW for one-time treatment:
 
Elivaldogene autotemcel meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
1. Individual is a biologic male between 4 and 17 years old at the time of infusion of elivaldogene autotemcel (FDA, 2022); AND
2. Evidence of early, active cerebral adrenoleukodystrophy (CALD) is demonstrated by ALL of the following (FDA, 2022):
a. Neurologic function score, NFS ≤ 1; AND
b. Gadolinium enhancement on MRI of demyelinating lesions; AND
c. Loes score 0.5-9 on the 34-point scale; AND
d. Elevated very long chain fatty acids (VLCFA) values (see policy guidelines); AND
e. Confirmed mutation in the ABCD1 gene; AND
f. Diagnosis of CALD is not secondary to head trauma (FDA, 2022); AND
3. Individual does not have a full ABCD1 gene deletion (FDA, 2022); AND
4. Elivaldogene autotemcel must be prescribed by or in consultation with a physician who specializes in the treatment of adrenoleukodystrophy (ALD); AND
5. Individual must have documented evidence of consultation with a hematologist-oncologist physician to assess evidence of any pre-existing myelodysplastic syndrome (MDS) findings and counsel about the long-term risks of MDS; AND
6. Individual is a candidate for HSCT (see policy guidelines); AND
7. Individual does not have/has not had any of the following (NEJM, 2017):
a. Prior allo-HSCT; OR
b. Prior gene therapy; OR
c. A willing 10/10 HLA-matched sibling donor for allo-HSCT (NEJM, 2017); OR
d. Any clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or prion associated infection, including but limited to positive human immunodeficiency virus (HIV-1 or HIV-2), human T lymphotropic virus 1 (HTLV-1), active hepatitis B virus, and hepatitis C virus (NEJM, 2017); AND
8. Will not be used for any condition associated with adrenoleukodystrophy including but not limited to the following:
a. Adrenomyeloneneuropathy (AMN); AND
b. Adult CALD; AND
c. Addison's-only ALD; AND
9. Must be dosed in accordance with the FDA label
 
Policy Guidelines
 
These are the specific values for the VLCFAs in males with CALD (with normal values in parentheses):
    • C26:0, 1.30 + 0.45 (normal: 0.23 + 0.09)
    • C24:0/C22:0, 1.71 + 0.23 (normal: 0.84 + 0.10)
    • C26:0/C22:0, 0.07 + 0.03 (normal: 0.01 + 0.004)
 
Lorenzo’s oil, a mixture of erucic/oleic acids, can normalize VLCFA levels. Erucic acid (C22:1) levels are usually reported when measuring VLCFA levels. Certain oils, such as mustard seed oil, have high levels of erucic acid and can lead to an elevation of VLCFAs.
 
Considerations for HSCT candidacy (the following should only be used as a guide to assess any pre-existing conditions that may increase potential risks of treatment and is not intended to exclude an individual from coverage of elivaldogene autotemcel unless an individual is identified as ineligible for HSCT):
 
1. Hematological compromise as evidenced by (NEJM, 2017):
a. Peripheral blood absolute neutrophil count (ANC) < 1500 cells/cubed millimeters
b. Platelet count < 100,000 cells/cubed millimeters
c. Hemoglobin < 10 g/dL
d. Uncorrected bleeding disorder
2. Hepatic compromise as evidenced by (NEJM, 2017):
a. Aspartate transaminase (AST) value > 2.5 X upper limit of normal (ULN)
b. Alanine transaminase (ALT) value > 2.5 X ULN
c. Total bilirubin value > 3.0 mg/dL, except if there is a diagnosis of Gilbert's Syndrome and the individual is otherwise stable
3. Renal compromise as evidenced by baseline estimated glomerular filtration rate of < 70 mL/min/1.73 square meters or actual or calculated creatinine clearance (CrCl) < 50 mL/min (NEJM, 2017)
4. Cardiac compromise as evidenced by left ventricular ejection fraction (LVEF) < 40% (NEJM, 2017)
5. Immediate family member (i.e., parent or siblings) with a known Familial Cancer Syndrome (Including but not limited to hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome and family adenomatous polyposis) (NEJM, 2017)
6. Any condition(s) that are contraindicated for continued MRI studies (NEJM, 2017)
7. Any contraindications to the use of Granulocyte Colony-Stimulating Factor (G-CSF) or plerixafor during the mobilization of hematopoietic stem cells, and any contraindications to use the use of busulfan or fludarabine, including known hypersensitivity to the active substances or to any of the excipients in their formulations (NEJM, 2017)  
 
Dosage and Administration
Dosing per FDA Label
 
The minimum recommended dose of elivaldogene autotemcel is 5.0 X 1 million CD34+ cells/kg. The dose is calculated based on the individual's weight prior to first apheresis. Elivaldogene autotemcel is administered as a single autologous intravenous infusion by a healthcare professional in the hospital inpatient setting.
 
Elivaldogene autotemcel is available as a cell suspension for intravenous infusion. Elivaldogene autotemcel is composed of one or two infusion bags which contain 4 to 30 X 1 million cells/mL suspended in cryopreservation solution. Each infusion bag contains approximately 20 mL of elivaldogene autotemcel. ABCBS will consider “a single infusion” the sum or one or more IV bags of cellular product. Any attempt to bill these as separate treatments or infusions regardless of date or site of service will be denied.
 
Dosing limits: one injection per lifetime.  
 
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Elivaldogene autotemcel, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, elivaldogene autotemcel, for any indication or circumstance not described above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Other Considerations
 
Elivaldogene autotemcel was not studied in combination with statins, Lorenzo's Oil, or dietary regimens used to lower VLFCA levels. Prescriber’s discretion in advised regarding the continuation of VLFCA lowering treatments after elivaldogene autotemcel administration.
 
Where feasible, the individual’s vaccination should be up to date with all age-appropriate vaccinations before elivaldogene autotemcel administration.
 
Where feasible, the individual should receive periodical monitoring for hematological malignancies, including Myelodysplastic Syndrome (MDS).
 
Final administration of elivaldogene autotemcel may be limited based on the myeloablative and lymphodepleting conditioning requirements.
 
Per prescribing information, individuals should not take antiretroviral medication for at least one month prior to initiating medication for stem cell mobilization and for the expected duration for elimination of the medications, and until all cycles of apheresis are complete.
 
Effective January 2024 to December 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
STANDARD REVIEW for one-time treatment for 6 months:
 
Elivaldogene autotemcel meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
1. Individual is a biologic male between 4 and 17 years old at the time of infusion of elivaldogene autotemcel (FDA, 2022); AND  
2. Evidence of early, active cerebral adrenoleukodystrophy (CALD) is demonstrated by ALL of the following (FDA, 2022):
a. Neurologic function score, NFS ≤ 1; AND  
b. Gadolinium enhancement on MRI of demyelinating lesions; AND
c. Loes score 0.5-9 on the 34-point scale; AND  
d. Elevated very long chain fatty acids (VLCFA) values (see policy guidelines); AND  
e. Confirmed mutation in the ABCD1 gene; AND  
f. Diagnosis of CALD is not secondary to head trauma (FDA, 2022); AND  
3. Individual does not have a full ABCD1 gene deletion (FDA, 2022); AND  
4. Elivaldogene autotemcel must be prescribed by or in consultation with a physician who specializes in the treatment of adrenoleukodystrophy (ALD); AND  
5. Individual must have documented evidence of consultation with a hematologist-oncologist physician to assess evidence of any pre-existing myelodysplastic syndrome (MDS) findings and counsel about the long-term risks of MDS; AND  
6. Individual is a candidate for HSCT (see policy guidelines); AND
7. Individual does not have/has not had any of the following (NEJM, 2017):
a. Prior allo-HSCT; OR  
b. Prior gene therapy; OR  
c. A willing 10/10 HLA-matched sibling donor for allo-HSCT (NEJM, 2017); OR  
d. Any clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or prion associated infection, including but limited to positive human immunodeficiency virus (HIV-1 or HIV-2), human T lymphotropic virus 1 (HTLV-1), active hepatitis B virus, and hepatitis C virus (NEJM, 2017); AND
8. Will not be used for any condition associated with adrenoleukodystrophy including but not limited to the following:
a. Adrenomyeloneneuropathy (AMN); AND
b. Adult CALD; AND
c. Addison's-only ALD; AND
9. Must be dosed in accordance with the FDA label
 
Policy Guidelines
 
These are the specific values for the VLCFAs in males with CALD (with normal values in parentheses):
    • C26:0, 1.30 + 0.45 (normal: 0.23 + 0.09)
    • C24:0/C22:0, 1.71 + 0.23 (normal: 0.84 + 0.10)
    • C26:0/C22:0, 0.07 + 0.03 (normal: 0.01 + 0.004)
 
Lorenzo’s oil, a mixture of erucic/oleic acids, can normalize VLCFA levels. Erucic acid (C22:1) levels are usually reported when measuring VLCFA levels. Certain oils, such as mustard seed oil, have high levels of erucic acid and can lead to an elevation of VLCFAs.
 
Considerations for HSCT candidacy (the following should only be used as a guide to assess any pre-existing conditions that may increase potential risks of treatment and is not intended to exclude an individual from coverage of elivaldogene autotemcel unless an individual is identified as ineligible for HSCT):
 
1. Hematological compromise as evidenced by (NEJM, 2017):
a. Peripheral blood absolute neutrophil count (ANC) < 1500 cells/mm3
b. Platelet count < 100,000 cells/mm3
c. Hemoglobin < 10 g/dL
d. Uncorrected bleeding disorder
2. Hepatic compromise as evidenced by (NEJM, 2017):
a. Aspartate transaminase (AST) value > 2.5×upper limit of normal (ULN)
b. Alanine transaminase (ALT) value > 2.5×ULN
c. Total bilirubin value > 3.0 mg/dL, except if there is a diagnosis of Gilbert's Syndrome and the individual is otherwise stable
3. Renal compromise as evidenced by baseline estimated glomerular filtration rate of < 70 mL/min/1.73 square meters or actual or calculated creatinine clearance (CrCl) < 50 mL/min (NEJM, 2017)
4. Cardiac compromise as evidenced by left ventricular ejection fraction (LVEF) < 40% (NEJM, 2017)
5. Immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (Including but not limited to hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome and family adenomatous polyposis) (NEJM, 2017)  
6. Any condition(s) that are contraindicated for continued MRI studies (NEJM, 2017)
7. Any contraindications to the use of Granulocyte Colony-Stimulating Factor (G-CSF) or plerixafor during the mobilization of hematopoietic stem cells, and any contraindications to use the use of busulfan or fludarabine, including known hypersensitivity to the active substances or to any of the excipients in their formulations (NEJM, 2017)  
 
Dosage and Administration
Dosing per FDA Label
 
The minimum recommended dose of elivaldogene autotemcel is 5.0 × 10 to the6th power CD34+ cells/kg. The dose is calculated based on the individiual's weight prior to first apheresis. Elivaldogene autotemcel is administered as a single autologous intravenous infusion by a healthcare professional in the hospital inpatient setting.
 
Elivaldogene autotemcel is available as a cell suspension for intravenous infusion. Elivaldogene autotemcel is composed of one or two infusion bags which contain 4 to 30 × 10 to the 6th power cells/mL suspended in cryopreservation solution. Each infusion bag contains approximately 20 mL of elivaldogene autotemcel. ABCBS will consider “a single infusion” the sum or one or more IV bags of cellular product. Any attempt to bill these as separate treatments or infusions regardless of date or site of service will be denied.
 
Dosing limits: one injection per lifetime.  
 
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Elivaldogene autotemcel, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, elivaldogene autotemcel, for any indication or circumstance not described above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Other Considerations
 
Elivaldogene autotemcel was not studied in combination with statins, Lorenzo's Oil, or dietary regimens used to lower VLFCA levels. Prescriber’s discretion in advised regarding the continuation of VLFCA lowering treatments after elivaldogene autotemcel administration.
 
Where feasible, the individual’s vaccination should be up to date with all age-appropriate vaccinations before elivaldogene autotemcel administration.
 
Where feasible, the individual should receive periodical monitoring for hematological malignancies, including Myelodysplastic Syndrome (MDS).
 
Final administration of elivaldogene autotemcel may be limited based on the myeloablative and lymphodepleting conditioning requirements.
 
Per prescribing information, individuals should not take antiretroviral medication for at least one month prior to initiating medication for stem cell mobilization and for the expected duration for elimination of the medications, and until all cycles of apheresis are complete.
 
Effective February 1, 2023 to December 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
STANDARD REVIEW for one-time treatment for 6 months:
 
Elivaldogene autotemcel meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
    1. Individual is a biologic male between 4 and 17 years old at the time of infusion of elivaldogene autotemcel (FDA, 2022); AND  
    2. Evidence of early, active cerebral adrenoleukodystrophy (CALD) is demonstrated by ALL of the following (FDA, 2022):
a. Neurologic function score, NFS ≤ 1; AND  
b. Gadolinium enhancement on MRI of demyelinating lesions; AND
c. Loes score 0.5-9 on the 34-point scale; AND  
d. Elevated very long chain fatty acids (VLCFA) values (see policy guidelines); AND  
e. Confirmed mutation in the ABCD1 gene; AND  
f. Diagnosis of CALD is not secondary to head trauma (FDA, 2022); AND  
3. Individual does not have a full ABCD1 gene deletion (FDA, 2022); AND  
4. Elivaldogene autotemcel must be prescribed by or in consultation with a physician who specializes in the treatment of adrenoleukodystrophy (ALD); AND  
5. Individual must have documented evidence of consultation with a hematologist-oncologist physician to assess evidence of any pre-existing myelodysplastic syndrome (MDS) findings and counsel about the long-term risks of MDS; AND  
6. Individual is a candidate for HSCT (see policy guidelines); AND
7. Individual does not have/has not had any of the following (NEJM, 2017):
a. Prior allo-HSCT; OR  
b. Prior gene therapy; OR  
c. A willing 10/10 HLA-matched sibling donor for allo-HSCT (NEJM, 2017); OR  
d. Any clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or prion associated infection, including but limited to positive human immunodeficiency virus (HIV-1 or HIV-2), human T lymphotropic virus 1 (HTLV-1), active hepatitis B virus, and hepatitis C virus (NEJM, 2017); AND
8. Must be dosed in accordance with the FDA label
 
Policy Guidelines
 
These are the specific values for the VLCFAs in males with CALD (with normal values in parentheses):
    • C26:0, 1.30 + 0.45 (normal: 0.23 + 0.09)
    • C24:0/C22:0, 1.71 + 0.23 (normal: 0.84 + 0.10)
    • C26:0/C22:0, 0.07 + 0.03 (normal: 0.01 + 0.004)
 
Lorenzo’s oil, a mixture of erucic/oleic acids, can normalize VLCFA levels. Erucic acid (C22:1) levels are usually reported when measuring VLCFA levels. Certain oils, such as mustard seed oil, have high levels of erucic acid and can lead to an elevation of VLCFAs.
 
Considerations for HSCT candidacy (the following should only be used as a guide to assess any pre-existing conditions that may increase potential risks of treatment and is not intended to exclude a member from coverage of elivaldogene autotemcel unless a member is identified as ineligible for HSCT):
    1. Hematological compromise as evidenced by (NEJM, 2017):
a. Peripheral blood absolute neutrophil count (ANC) < 1500 cells/mm3
b. Platelet count < 100,000 cells/mm3
c. Hemoglobin < 10 g/dL
d. Uncorrected bleeding disorder
2. Hepatic compromise as evidenced by (NEJM, 2017):
a. Aspartate transaminase (AST) value > 2.5×upper limit of normal (ULN)
b. Alanine transaminase (ALT) value > 2.5×ULN
c. Total bilirubin value > 3.0 mg/dL, except if there is a diagnosis of Gilbert's Syndrome and the individual is otherwise stable
3. Renal compromise as evidenced by baseline estimated glomerular filtration rate of < 70 mL/min/1.73 square meters or actual or calculated creatinine clearance (CrCl) < 50 mL/min (NEJM, 2017)
4. Cardiac compromise as evidenced by left ventricular ejection fraction (LVEF) < 40% (NEJM, 2017)
5. Immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (Including but not limited to hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome and family adenomatous polyposis) (NEJM, 2017)  
6. Any condition(s) that are contraindicated for continued MRI studies (NEJM, 2017)
7. Any contraindications to the use of Granulocyte Colony-Stimulating Factor (G-CSF) or plerixafor during the mobilization of hematopoietic stem cells, and any contraindications to use the use of busulfan or fludarabine, including known hypersensitivity to the active substances or to any of the excipients in their formulations (NEJM, 2017)  
 
Dosage and Administration
Dosing per FDA Label
 
The minimum recommended dose of elivaldogene autotemcel is 5.0 × 1 million CD34+ cells/kg. The dose is calculated based on the patient’s weight prior to first apheresis. Elivaldogene autotemcel is administered as a single autologous intravenous infusion by a healthcare professional in the hospital inpatient setting.
 
Elivaldogene autotemcel is available as a cell suspension for intravenous infusion. Elivaldogene autotemcel is composed of one or two infusion bags which contain 4 to 30 × 1 million cells/mL suspended in cryopreservation solution. Each infusion bag contains approximately 20 mL of elivaldogene autotemcel. ABCBS will consider “a single infusion” the sum or one or more IV bags of cellular product. Any attempt to bill these as separate treatments or infusions regardless of date or site of service will be denied.
 
Dosing limits: one injection per lifetime.  
 
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Elivaldogene autotemcel, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes or for any other condition associated with adrenoleukodystrophy including but not limited to adrenomyeloneuropathy (AMN), adult CALD, and Addison’s-only ALD.
 
For members with contracts without primary coverage criteria, elivaldogene autotemcel, for any indication or circumstance not described above or for any other condition associated with adrenoleukodystrophy including but not limited to adrenomyeloneuropathy (AMN), adult CALD, and Addison’s-only ALD, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Other Considerations
 
Elivaldogene autotemcel was not studied in combination with statins, Lorenzo's Oil, or dietary regimens used to lower VLFCA levels. Prescriber’s discretion in advised regarding the continuation of VLFCA lowering treatments after elivaldogene autotemcel administration.
 
Where feasible, the individual’s vaccination should be up to date with all age-appropriate vaccinations before elivaldogene autotemcel administration.
 
Where feasible, the individual should receive periodical monitoring for hematological malignancies, including Myelodysplastic Syndrome (MDS).
 
Final administration of elivaldogene autotemcel may be limited based on the myeloablative and lymphodepleting conditioning requirements.
 
Per prescribing information, individuals should not take antiretroviral medication for at least one month prior to initiating medication for stem cell mobilization and for the expected duration for elimination of the medications, and until all cycles of apheresis are complete.
Rationale:
The safety and efficacy of elivaldogene autotemcel were assessed in two 24-month, open-label, single-arm studies in males aged 17 years and younger with early, active CALD as defined by Loes score between 0.5 and 9 (inclusive) and gadolinium enhancement (GdE+) on MRI, as well as a neurologic function score (NFS) of ≤ 1. Study 1, ALD-102 (NCT01896102), is complete and Study 2, ALD-104 (NCT03852498), is ongoing at the time of this review.
 
Study 1, N=32, was a phase 2/3 study to investigate the primary outcome of percentage of patients alive and without any of the six major functional disabilities at 24 months post-administration. 17 boys received elivaldogene autotemcel gene therapy. The median age was 6 years old (range 4-13 years old), median Loes score was 2.0, median NFS 0, and median dose of elivaldogene autotemcel of 10.5 x 106 CD34+ cells/kg. Results of Study 1 revealed that 15 of the 17 patients (88%) were alive and free of major functional disability, with minimal clinical symptoms. One patient, who had had rapid neurologic deterioration, had died from disease progression. Another patient, who had had evidence of disease progression on MRI, had withdrawn from the study to undergo allo-HSCT and later died from transplantation-related complications. No toxic effects related to the infusion of elivaldogene autotemcel were reported, including graft failure, GVHD, or transplantation-related death. Most adverse events associated with the treatment occurred during the conditioning phase or the first two weeks after the infusion, and they were generally consistent with the adverse events associated with myeloablative chemotherapy. The most common non-laboratory adverse reactions (≥30% incidence) were mucositis, nausea, febrile neutropenia, vomiting, alopecia, decreased appetite, catheter site pain, abdominal pain, and constipation. 14 patients from this study were enrolled in the long-term follow-up study, LTF-304 (NCT02698579), which is enrolling participants at the time of this review (NEJM, 2017).
 
Study 2, N=35, is a phase 3 study to investigate the primary outcome of percentage of patients alive and without any of the six major functional disabilities at 24 months post-administration. The estimated study completion date is February 2024 (ClinicalTrials.gov, 2022).
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2024. No new literature was identified that would prompt a change in the coverage statement.
 
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2025. No new literature was identified that would prompt a change in the coverage statement.
 
Clinical Trials
 
CPT/HCPCS:
C9399Unclassified drugs or biologicals
J3590Unclassified biologics
References: A Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD). ClinicalTrials.gov identifier: NCT03852498. Updated April 4, 2022. https://www.clinicaltrials.gov/ct2/show/NCT03852498. Accessed November 16, 2022.

Chiesa R, et al.(2022) Variables affecting outcomes after allogeneic hematopoietic stem cell transplant for cerebral adrenoleukodystrophy. Blood Adv. 2022;6(5):1512-1524. doi:10.1182/bloodadvances.2021005294

Eichler, Florian et al.(2017) “Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy.” The New England journal of medicine (NEJM) vol. 377,17 (2017): 1630-1638. doi:10.1056/NEJMoa1700554. Accessed November 15, 2022.

Our focus: Cerebral Adrenoleukodystrophy (CALD): Bluebird bio. bluebird bio | Pioneering Gene Therapies. https://www.bluebirdbio.com/our-focus/cerebral-adrenoleukodystrophy. Accessed November 15, 2022.

U.S. Food and Drug Administration (FDA).(2022) Skysona. Prescribing Information. https://www.fda.gov/media/161640/download. Accessed November 15, 2022.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association.