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Table 65: Enzyme and Metabolic Disorder Therapies


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Drug Category: Endocrine and Metabolic Agents

Medication Class/Individual Agents: Enzyme and Metabolic Disorder Therapies

I. Prior-Authorization Requirements

 Enzyme and Metabolic Disorder Therapies – Injectable Agents

Clinical Notes

Drug Details

Drug Generic Name

Drug Brand Name

PA
Status

Drug
Notes

agalsidase beta Fabrazyme PA  
alglucosidase alfa Lumizyme PA  
asfotase alfa Strensiq PA  
avalglucosidase alfa-ngpt Nexviazyme PA  
elapegademase-lvlr Revcovi PA  
elosulfase alfa Vimizim PA  
galsulfase Naglazyme PA  
idursulfase Elaprase PA  
imiglucerase Cerezyme PA  
laronidase Aldurazyme PA  
pegvaliase-pqpz Palynziq PA  
taliglucerase alfa Elelyso PA  
velaglucerase alfa Vpriv PA  
vestronidase alfa-vjbk Mepsevii PA  

Please note: In the case where the prior authorization (PA) status column indicates PA, both the brand and generic (if available) require PA. Typically, the generic is preferred when available unless the brand-name drug appears on the MassHealth Brand Name Preferred Over Generic Drug List. In general, when requesting the non-preferred version, whether the brand or generic, the prescriber must provide medical records documenting an inadequate response or adverse reaction to the preferred version, in addition to satisfying the criteria for the drug itself.

  • Lysosomal storage disorders are caused by a deficiency or absence of required enzymes. The consequence is an accumulation of compounds that are normally degraded, causing cell and organ dysfunction. Before the development of enzyme replacement therapy, management of these conditions consisted of supportive care and treatment of the complications.
  • A number of exogenously supplied enzymes are available for lysosomal storage disorders, including adenosine deaminase (ADA) deficiency, Gaucher disease, Fabry disease, Hunter syndrome, hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthetase, hypophosphatasia, lysosomal acid lipase deficiency, mucopolysaccharidosis type I, IVA, VI, and VII, and Pompe disease.
  • Pancreatic enzyme replacement is indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis or other conditions. Multiple formulations of pancreatic enzymes exist with different combinations of lipase, protease, and amylase; however, these enzymes may differ in their effects. Members should be reevaluated after any changes in enzyme preparation or dose.
  • Molybdenum cofactor deficiency (MoCD) is a rare genetic disorder that results from one of several single gene defects in the biosynthetic pathway of molybdenum cofactor. About two-thirds of members have MoCD type A, which involves mutations in molybdenum cofactor synthesis gene 1 (MOSC1). Prior to the approval of fosdenopterin, the only available treatment options included supportive care and therapies directed towards complications arising from the disease. 
  • Pyruvate kinase deficiency is an inherited red blood cell enzyme disorder that causes chronic hemolysis. Affected individuals are either homozygous for a single pathogenic mutation or compound heterozygous for two different pathogenic variants affecting the function of the pyruvate kinase enzyme in red blood cells and liver. Mitapivat is a pyruvate kinase activator that acts by allosterically binding to the pyruvate kinase tetramer and increasing pyruvate kinase activity.
  • PIK3CA-Related Overgrowth Spectrum (PROS) is considered a rare disease that includes a group of genetic disorders, which leads to overgrowth of various body parts due to PIK3CA mutations. Alpelisib is small-molecule inhibitor of phosphatidylinositol-3 kinase (PI3K). Mutations in the gene for PI3K lead to PI3Ka and Akt activation, tumor generation, and cellular transformation. Activating these mutations lead to a range of malformations and overgrowths known as PROS. Alpelisib can inhibit the phosphorylation of PI3K and Akt to prevent further activity in the pathway.
 

 Enzyme and Metabolic Disorder Therapies – Oral Agents

Drug Details

Drug Generic Name

Drug Brand Name

PA
Status

Drug
Notes

alpelisib-Vijoice Vijoice PA  
carglumic acid Carbaglu PA   BP, A90
glycerol phenylbutyrate Ravicti PA  
migalastat Galafold PA  
mitapivat Pyrukynd PA  
pancrelipase-Creon DR Creon DR test  
pancrelipase-Pancreaze DR Pancreaze DR test  
pancrelipase-Pertzye DR Pertzye DR test  
pancrelipase-Viokace Viokace test  
pancrelipase-Zenpep DR Zenpep DR test  
sapropterin Kuvan PA  
triheptanoin Dojolvi PA  

 Enzyme and Metabolic Disorder Therapies – Substrate Replacement/Reduction Therapies

Drug Details

Drug Generic Name

Drug Brand Name

PA
Status

Drug
Notes

eliglustat Cerdelga PA  
fosdenopterin Nulibry PA  
miglustat Zavesca PA   BP
sebelipase alfa Kanuma PA  
Table Footnotes
BP Brand Preferred over generic equivalents. In general, MassHealth requires a trial of the preferred drug or clinical rationale for prescribing the non-preferred drug generic equivalent.
 
A90 Allowable 90-day supply. Dispensing in up to a 90-day supply is allowed. May not include all strengths or formulations. Quantity limits and other restrictions may apply.
 

II. Therapeutic Uses

FDA-approved, for example: 

  • Adenosine deaminase severe combined immunodeficiency (ADA-SCID) (Revcovi)
  • Fabry disease (Fabrazyme, Galafold)
  • Gaucher Disease Type 1 (Cerdelga, Cerezyme, Elelyso, miglustat, Vpriv)
  • Hemolytic anemia with pyruvate kinase deficiency (Pyrukynd)
  • Hunter Syndrome (Elaprase)
  • Hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthetase (NAGS) (carglumic acid)
  • Hyperammonemia due to propionic aciduria (PA) or methylmalonic aciduria (MMA) (carglumic acid)
  • Hypophosphatasia (Strensiq)
  • Long-chain fatty acid oxidation disorders (LC-FAOD) (Dojolvi)
  • Lysosomal acid lipase deficiency (Kanuma)
  • Molybdenum cofactor deficiency (MoCD) Type A (Nulibry)
  • Mucopolysaccharidosis I (Aldurazyme)
  • Mucopolysaccharidosis IVA (Morquio A syndrome) (Vimizim)
  • Mucopolysaccharidosis VI (Naglazyme)
  • Mucopolysaccharidosis VII (Sly syndrome) (Mepsevii)
  • Phenylketonuria (Palynziq, sapropterin)
  • PIK3CA-Related Overgrowth Spectrum (PROS) (Vijoice)
  • Pompe disease (Lumizyme, Nexviazyme)
  • Urea cycle disorder (Ravicti)

Note: The above list may not include all FDA-approved indications.

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III.  Evaluation Criteria for Approval

Please note: In the case where the prior authorization (PA) status column indicates PA, both the brand and generic (if available) require PA. Typically, the generic is preferred when available unless the brand-name drug appears on the MassHealth Brand Name Preferred Over Generic Drug List. In general, when requesting the non-preferred version, whether the brand or generic, the prescriber must provide medical records documenting an inadequate response or adverse reaction to the preferred version, in addition to satisfying the criteria for the drug itself.

  • All PA requests must include clinical diagnosis, drug name, dose, and frequency.
  • Dispensing in a 90-day supply of medication may be mandated or allowable for agents in this therapeutic class (designated by M90 or A90, respectively, in the Drug Notes section above). Applicable quantity limits are described below as units per day, per month, per 28 days, or as clinically appropriate, and may be extrapolated for fills of longer day supply. 
  • A preferred drug may be designated for this therapeutic class. In general, MassHealth requires a trial of the preferred drug or clinical rationale for prescribing a non-preferred drug within a therapeutic class. Additional information about these agents, including PA requirements and preferred products, can be found within the MassHealth Drug List at www.mass.gov/druglist.
  • For recertification requests, approval may require submission of additional documentation including, but not limited to, documentation of: some or all criteria for the original approval; response to therapy; clinical rationale for continuation of use; status of member’s condition; appropriate diagnosis; appropriate age; appropriate dose, frequency, and duration of use for requested medication; complete treatment plan; current laboratory values; and member’s current weight.
  • Additional criteria may apply, depending upon the member’s condition and requested medication (see below).

      

Aldurazyme

  • Documentation of all of the following is required:
    • appropriate diagnosis; and
    • results from genetic testing showing mutations in IDUA gene or an enzyme assay test showing reduced lysosomal alpha-L-iduronidase activity in peripheral blood leukocytes, plasma, or cultured fibroblasts; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.

carglumic acid

  • Documentation of all of the following is required for hyperammonemia due to NAGS deficiency:
    • appropriate diagnosis; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • appropriate dosing; and
    • results from genetic test or an enzyme assay test supporting the diagnosis.
  • Documentation of all of the following is required for hyperammonemia due to PA or MMA:
    • appropriate diagnosis; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • appropriate dosing; and
    • results from genetic testing, medical records, or lab results supporting the diagnosis; and 
    • elevated ammonia levels > 60 μmol/L.

Cerdelga

  • Documentation of all of the following is required:
    • appropriate diagnosis; and
    • member is ≥ 18 years of age; and
    • results from enzyme assay test showing reduced activity of glucocerebrosidase; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member is not currently receiving enzyme replacement therapy.

Cerezyme and Vpriv

  • Documentation of all of the following is required:
    • appropriate diagnosis; and
    • results from genetic test confirming mutation in GBA gene or an enzyme assay test showing reduced activity of the enzyme glucocerebrosidase; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.

Dojolvi

  • Documentation of all of the following is required: 
    • diagnosis of long-chain fatty acid oxidation disorders (LC-FAOD); and
    • results from genetic testing or molecular analysis to confirm diagnosis (e.g., CPT I or II, LCHAD, TFP, VLCAD deficiency); and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • trial with a diet consisting of low-fat, high-carbohydrates, and avoidance of fasting; and
    • member's current caloric intake.

Elaprase

  • Documentation of all of the following is required: 
    • appropriate diagnosis; and
    • results from genetic testing confirming mutation in IDS gene or iduronate-2-sulfatase assay test showing reduced or absent activity in the serum, white blood cells, or fibroblasts; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.

Elelyso

  • Documentation of all of the following is required: 
    • appropriate diagnosis; and
    • results from genetic test confirming mutation in GBA gene or an enzyme assay test showing reduced activity of the enzyme glucocerebrosidase; and
    • member is ≥ four years of age; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.

Fabrazyme

  • Documentation of all of the following is required: 
    • appropriate diagnosis; and
    • one of the following:
      • results from an enzyme assay test showing reduced or absent α-galactosidase A (α-GAL) enzyme activity in plasma, leukocytes, tears, or biopsied tissue; or
      • Genetic testing confirming mutation in GAL gene; or
      • Biomarker demonstrating an increase in Gb3 concentration; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.

Galafold

  • Documentation of all of the following is required: 
    • appropriate diagnosis; and
    • member is ≥ 18 years of age; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • results from an enzyme assay test showing reduced or absent α-galactosidase A (α-GAL) enzyme activity in plasma, leukocytes, tears, or biopsied tissue; and
    • member has GLA variants which are amenable to treatment with the requested agent; and
    • requested quantity is ≤ 15 units/30 days.

Kanuma

  • Documentation of all of the following is required:
    • diagnosis of lysosomal acid lipase deficiency; and
    • one of the following:
      • lab assay documenting low lysosomal acid lipase activity; or
      • genetic testing confirming full or partial loss of LAL gene; and
    • prescriber is a specialist in genetic or metabolic diseases or consult notes from a specialist are provided; and
    • member's current weight.

Lumizyme

  • Documentation of all of the following is required: 
    • appropriate diagnosis; and
    • one of the following:
      • results from acid maltase enzyme alpha-glucosidase (GAA) assay test showing reduced or absent activity from cultured skin fibroblasts; or
      • lymphocyte testing; or
      • blood spot assay; or
      • genetic testing confirming mutation in GAA gene; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.

Mepsevii

  • Documentation of all of the following is required: 
    • appropriate diagnosis; and
    • results from genetic testing showing mutations in the beta glucuronidase gene; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.

miglustat

  • Documentation of all of the following is required:
    • appropriate diagnosis; and
    • member is ≥ 18 years of age; and
    • results from enzyme assay test showing reduced activity of glucocerebrosidase; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • contraindication to enzyme replacement therapy.

Naglazyme

  • Documentation of all of the following is required: 
    • appropriate diagnosis; and
    • results from an enzyme assay test showing reduced arylsulfatase B (ASB) enzyme activity in leukocytes or fibroblasts along with elevated urine glycosaminoglycan (GAG) levels; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.
     

Nexviazyme

  • Documentation of all of the following is required:
    • appropriate diagnosis; and
    • one of the following:
      • results from GAA assay test showing reduced or absent activity from cultured skin fibroblasts; or
      • lymphocyte testing; or
      • blood spot assay; or
      • genetic testing confirming mutation in GAA gene; and
    • member is ≥ one year of age; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight; and
    • for members weighing < 30 kg, contraindication to Lumizyme.

Nulibry

  • Documentation of all of the following is required:
    • appropriate diagnosis confirmed by genetic testing; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • appropriate dosing; and
    • member's current weight.

Palynziq

  • Documentation of all of the following is required:
    • appropriate diagnosis; and
    • member is ≥ 18 years of age; and
    • results from genetic testing or molecular analysis to confirm diagnosis; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • blood phenylalanine concentrations > 600 micromol/L; and
    • medication will be used in conjunction with a phenylalanine-restricted diet; and
    • inadequate response, adverse reaction, or contraindication to sapropterin.

Pyrukynd

  • Documentation of all of the following is required: 
    • diagnosis of hemolytic anemia with pyruvate kinase deficiency; and
    • member is ≥ 18 years of age; and
    • results from genetic testing confirming mutation in PKLR gene or lab testing showing reduced or absent activity of pyruvate kinase; and
    • prescriber is a specialist in genetic diseases, hematology, or metabolic diseases or consultation notes from a specialist are provided; and
    • hemoglobin (Hb) ≤ 10 g/dL (dated within the last 60 days); and
    • requested quantity is ≤ two units/day.

Ravicti

  • Documentation of all of the following is required:
    • appropriate diagnosis; and
    • results from genetic test or an enzyme assay test supporting the diagnosis; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • appropriate dosing; and
    • inadequate response, adverse reaction, or contraindication to sodium phenylbutyrate.

Revcovi

  • Documentation of all of the following is required:
    • appropriate diagnosis; and
    • laboratory results documenting one of the following:
      • absent ADA enzymatic activity in lysed erythrocytes; or 
      • elevated levels of adenosine and deoxyadenosine in the urine and plasma; or 
      • a marked increase in deoxyadenosine triphosphate (dATP) levels in erythrocyte lysates; or 
      • a significant decrease in ATP concentration in red blood cells; or 
      • absent or extremely low levels of N adenosylhomocysteine hydrolase in red blood cells; or 
      • severe T cell deficiency manifested by lymphopenia and poor T cell responses to mitogens and antigens; or 
      • absent thymic shadow on chest radiograph; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.

sapropterin

  • Documentation of all of the following is required:
    • appropriate diagnosisand
    • results from molecular analysis to confirm diagnosis; and
    • documentation that medication will be used in conjunction with a phenylalanine-restricted diet; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.

Strensiq

  • Documentation of all of the following is required:
    • diagnosis of perinatal-onset, infantile-onset, or juvenile-onset hypophosphatasia; and
    • genetic testing confirming mutation in ALPL gene; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.

Vijoice

  • Documentation of all of the following is required: 
    • diagnosis of PROS with congenital or early childhood onset; and
    • member is ≥ two years of age; and
    • overgrowth is sporadic and mosaic (i.e., patchy, irregular); and
    • results from genetic testing showing evidence of a mutation in the PIK3CA gene; and
    • appropriate dosing; and
    • medical records documenting one of the following:
      • spectrum categorization defined as having at least two of the following:
        • adipose, muscle, nerve, or skeletal overgrowth; or
        • capillary, venous, arteriovenous, or lymphatic vascular malformations; or
        • epidermal nevus; or
      • isolated features defined as having one of the following:
        • large isolated lymphatic malformation; or
        • isolated macrodactyly or overgrown splayed feet/hands, overgrown limbs; or
        • truncal adipose overgrowth; or
        • bilateral hemimegalencephaly/dysplastic megalencephaly/focal cortical dysplasia type 2; or
        • epidermal nevus; or
        • seborrheic keratoses; or
        • benign lichenoid keratoses.

Vimizim

  • Documentation of all of the following is required:
    • appropriate diagnosis; and
    • member is ≥ five years of age; and
    • results from an enzyme assay test showing reduced N-acetylgalactosamine-6-sulfatase activity in blood and/or skin cells; and
    • prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; and
    • member's current weight.


Original Effective Date: 11/2012

Last Revised Date: 09/2022


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Last updated 10/31/22

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