Drug and Biologic Coverage Policy Effective Date ........................................... 8/1/2021 Next Review Date… ..................................... 8/1/2022 Coverage Policy Number .................................. 1319 Enzyme Related Therapies Table of Contents Related Coverage Resources Coverage Policy ................................................... 1 Pharmacogenetic Testing FDA Approved Indications ................................... 4 Recommended Dosing ........................................ 5 General Background ............................................ 9 Coding/Billing Information .................................. 15 References ........................................................ 15 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations. Coverage Policy Enzyme related therapies include the following products: • agalsidase beta (Fabrazyme®) • alglucosidase alfa (Lumizyme®) • asfotase alfa (Strensiq®) • elapegademase-lvlr (Revcovi™) • eliglustat (Cerdelga®) • elosulfase alfa (Vimizim®) • galsulfase (Naglazyme®) • idursulfase (Elaprase®) • laronidase (Aldurazyme®) • migalastat (Galafold™) • miglustat (Zavesca®) • sacrosidase (Sucraid®) • sebelipase alfa (Kanuma®) • vestronidase alfa-vjbk (Mepsevii™) Enzyme related therapies are considered medically necessary when the following criteria are met: Page 1 of 16 Coverage Policy Number: 1319 Product Criteria for Use Aldurazyme Both of the following are met: (laronidase) • Mucopolysaccharidosis I (MPS I) with one of the following forms: o Severe mucopolysaccharidosis I (MPS I) o Attenuated mucopolysaccharidosis I (MPS I) with moderate to severe symptoms • Diagnosis documented by either of the following: o Demonstrated deficiency of alpha-L-iduronidase (for example, in peripheral blood leukocytes, plasma, or cultured fibroblasts) in the absence of a pseudodeficiency allele o Confirmation of biallelic pathogenic or likely pathogenic variants in the IDUA gene Cerdelga Individual is an adult and meets both of the following: (eliglustat) • Gaucher disease type 1 with diagnosis documented by either of the following: o Deficiency of glucosylceramidase [also known as acid β-glucosidase or glucocerebrosidase] in peripheral blood leukocytes or other nucleated cells o Confirmation of biallelic pathogenic variants in the GBA gene • One of the following: o CYP2D6 extensive metabolizer (EM) o CYP2D6 intermediate metabolizer (IM) o CYP2D6 poor metabolizer (PM) Eliglustat (Cerdelga) is considered experimental, investigational or unproven for ANY other use including the following: • CYP2D6 ultra-rapid metabolizers • CYP2D6 indeterminate metabolizers • Concomitant use with Zavesca or other treatments approved for Gaucher disease Elaprase Hunter syndrome [Mucopolysaccharidosis II (MPS II)] with diagnosis documented by (idursulfase) either of the following: • Deficiency of iduronidate 2-sulfatase in leukocytes, fibroblasts, or plasma and documentation of normal enzymatic activity of at least one other sulfatase in the same tissue type • Confirmation of a hemizygous pathogenic variant in the IDS gene Fabrazyme Fabry disease with diagnosis documented by ALL of the following: (agalsidase beta) • ONE of the following: o Deficiency of alpha-galactosidase A in plasma or peripheral leukocytes o Confirmation of a hemizygous pathogenic variant in the GLA gene • No concomitant use of Galafold (migalastat) Galafold All of the following are met: (migalastat) • Documented diagnosis of Fabry disease in an adult • Confirmed pathogenic or likely pathogenic variant in the GLA gene known to cause Fabry disease AND • Amenable mutation identified in GLA for use with Galafold • No concomitant use of Fabrazyme (agalsidase) Kanuma Lysosomal Acid Lipase (LAL) Deficiency (Wolman disease, cholesteryl ester storage (sebelipase alfa) disease [CESD]) with diagnosis documented by either of the following: • Deficiency of LAL in peripheral blood leukocytes, fibroblasts, or dried blood spots • Confirmation of biallelic pathogenic variants in the LIPA gene Lumizyme Pompe disease with diagnosis documented by either of the following: (alglucosidase alfa) • Deficiency of acid alpha-glucosidase in leukocytes or skin fibroblasts in the absence of a pseudodeficiency allele • Confirmation of biallelic pathogenic or likely pathogenic variants in the GAA gene Page 2 of 16 Coverage Policy Number: 1319 Product Criteria for Use Mepsevii Mucopolysaccharidosis VII (MPS VII, Sly syndrome) with diagnosis documented by (vestronidase alfa- either of the following: vjbk) • Deficiency of beta-glucuronidase in peripheral blood leukocytes or cultured fibroblasts • Genetic testing confirming mutations in the GUSB gene Naglazyme Mucopolysaccharidosis VI (MPS VI, Maroteaux-4 Lamy syndrome) with diagnosis (galsulfase) documented by either of the following: • Deficiency of N-acetylgalactosamine 4-sulfatase [ARSB] in leukocytes, fibroblasts, and dried blood spots • Confirmation of biallelic pathogenic variants in the ARSB gene Revcovi Adenosine deaminase severe combined immune deficiency (ADA-SCID) with (elapegademase-lvlr) diagnosis documented by either of the following: • Documented adenosine deaminase (ADA) deficiency (in hemolysates or in other cells if recent transfusion) consistent with the diagnosis of ADA-SCID • Confirmation of biallelic pathogenic variants or likely pathogenic in the ADA gene Strensiq All of the following are met: (asfotase alfa) • Documented diagnosis of perinatal/infantile-onset or juvenile-onset hypophosphatasia (HPP) • Total serum alkaline phosphatase (ALP) activity level below the lower limit of normal for age • Elevated serum pyridoxal 5’-phosphate (PLP) level • Radiologic evidence and clinical features of hypophosphatasia present • Confirmation of either a monoallelic or biallelic pathogenic variant(s) in the ALPL gene Sucraid BOTH of the following criteria are met: (sacrosidase) • Documentation of symptomatic congenital sucrose-isomaltase deficiency (CSID) (for example, diarrhea, bloating, abdominal cramping) • Diagnosis is confirmed by ONE of the following: o Endoscopic biopsy of the small bowel with disaccharidase levels consistent with CSID as evidenced by ALL of the following*: . Decreased (usually absent) sucrose (normal reference: greater than 25U/g protein) . Decreased to normal isomaltase (palatinase) (normal reference: greater than 5U/g protein) . Decreased maltase (normal reference: greater than 100 U/g protein) . Decreased to normal lactase (normal reference: greater than 15 U/g protein) o Documentation of homozygous or compound heterozygous pathogenic or likely pathogenic mutations in the sucrose-isomaltase (SI) gene *OR below the reporting lab’s normal reference range, if noted. Initial approval duration is 6 months. Reauthorization of Sucraid for 12 months requires evidence of beneficial clinical response. Vimizim Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) with diagnosis (elosulfase alfa) documented by either of the following: • Deficiency of N-acetylgalactosamine-6-sulphatase (GALNS) in cultured fibroblasts or leukocytes • Confirmation of biallelic pathogenic variants in the GALNS gene Zavesca Mild to moderate Gaucher disease type 1 in an adult and ALL of the following: (miglustat) • ONE of the following o Documented deficiency of glucosylceramidase (also known as acid β- glucosidase or glucocerebrosidase) in peripheral blood leukocytes or other nucleated Page 3 of 16 Coverage Policy Number: 1319 Product Criteria for Use o Confirmation of biallelic pathogenic variants in the GBA gene • Will be used as monotherapy • Not a candidate for enzyme replacement therapy AND • ONE of the following o History of beneficial clinical response to Zavesca o Documented failure/inadequate response, contraindication per FDA label,