MED.00142 Gene Therapy for Cerebral Adrenoleukodystrophy Form

This document addresses gene replacement therapy for cerebral adrenoleukodystrophy (CALD), a rare and life-threatening hereditary neurological disorder. One gene therapy product, elivaldogene autotemcel (Skysona^®), has been approved by the Food and Drug Administration (FDA) to treat individuals affected by CALD. Elivaldogene autotemcel is an autologous hematopoietic stem cell-based gene therapy that requires recipients to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for elivaldogene autotemcel manufacturing, as well as administration of full myeloablative conditioning before infusion of elivaldogene autotemcel.

Note: For other information regarding adrenoleukodystrophy treatments, please see:

• CG-MED-68 Therapeutic Apheresis
• TRANS.00029 Hematopoietic Stem Cell Transplantation for Genetic Diseases and Aplastic Anemias

Position Statement

Medically Necessary:

A one-time infusion of elivaldogene autotemcel is considered medically necessary when all of the following criteria are met:

1. The individual is in the early stages of cerebral adrenoleukodystrophy (CALD), as confirmed by the following:
   1. Elevated very long chain fatty acid levels; and
   2. Confirmation of the presence of an ABCD1 genetic mutation; and
   3. CALD-specific Neurological Function Scale (NFS) score of 0 or 1; and
   4. Active central nervous system (CNS) disease with demyelinating lesions demonstrated on brain gadolinium-enhanced MRI with Loes score between 0.5 and 9.0 on the 34-point scale; and
2. The individual is a candidate for an allogeneic hematopoietic cell transplantation, but ineligible due the absence of a donor*; and
3. The individual is 4 to 17 years of age; and
4. Absence of any clinically significant cardiovascular, hepatic, hematological, renal or pulmonary disease, or other disease or condition that poses a contraindication to the procedure, including myeloablative conditioning.

* Documentation that a suitable donor has not been identified, for example, a matched related donor or matched (HLA 8/8 or 7/8) unrelated donor.

Investigational and Not Medically Necessary:

Elivaldogene autotemcel is considered investigational and not medically necessary when the criteria above are not met, including for repeat infusions.