Mass General Brigham Health Plan enzyme therapy Prior Auth

Agent-specific Coverage Criteria

inv-01: General authorization rule

Authorization will be granted when ALL of the following are met:

General: Member meets all agent-specific criteria as listed in the policy (diagnosis confirmation, prescriber specialty/consultation, appropriate diagnostic testing, and current weight for dosing).

Authorizations for members new to the plan who are currently receiving treatment may be reviewed case-by-case.

inv-02: Aldurazyme (laronidase) — Initial criteria

Covered when ALL of the following are met

Aldurazyme: 1) Diagnosis of Mucopolysaccharidosis I (MPS I); 2) Results from genetic testing showing mutations in the IDUA gene or an enzyme assay demonstrating reduced alpha-L-iduronidase activity in peripheral blood leukocytes, plasma, or cultured fibroblasts; 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Member's current weight provided for dosing verification.

inv-03: Cerezyme (imiglucerase)

Covered when ALL of the following are met

Cerezyme: 1) Diagnosis of Gaucher disease (Type I).

Additional documentation (e.g., genetic testing or enzyme assay) is implied by general documentation requirements.

inv-04: Vpriv (velaglucerase) and Elelyso (taliglucerase alfa)

Covered when ALL of the following are met

Vpriv: 1) Diagnosis of Gaucher disease (Type I); 2) Results from genetic testing confirming a GBA mutation or an enzyme assay showing reduced glucocerebrosidase activity; 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Member's current weight provided for dosing verification.

Elelyso: 1) Diagnosis of Gaucher disease (Type I); 2) Results from genetic testing confirming a GBA mutation or an enzyme assay showing reduced glucocerebrosidase activity; 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Member is > 4 years of age; 5) Member's current weight provided for dosing verification.

inv-05: Elaprase (idursulfase)

Covered when ALL of the following are met

Elaprase: 1) Diagnosis of Hunter syndrome (MPS II); 2) Results from genetic testing confirming an IDS mutation or iduronate-2-sulfatase assay demonstrating reduced or absent activity in serum, white blood cells, or fibroblasts; 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Member's current weight provided for dosing verification.

inv-06: Elfabrio (pegunigalsidase) and Fabrazyme (agalsidase beta)

Covered when ALL of the following per agent are met

Elfabrio: 1) Diagnosis of Fabry disease; 2) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 3) Member's current weight provided for dosing verification where applicable.

Coverage for switching between agents may require inadequate response, adverse reaction, or contraindication to Fabrazyme.

Fabrazyme diagnostic options: Diagnosis of Fabry disease must be confirmed by ONE of: (a) enzyme assay demonstrating reduced or absent alpha-galactosidase (a-GAL) activity in plasma, leukocytes, tears, or biopsied tissue; (b) genetic testing confirming a GAL gene mutation; or (c) biomarker demonstrating increased Gb3 concentration; plus prescriber specialty and current weight for dosing.

inv-07: Kanuma (sebelipase alfa)

Covered when ALL of the following are met

Kanuma: 1) Diagnosis of lysosomal acid lipase deficiency; 2) ONE of: lab assay documenting low lysosomal acid lipase (LAL) activity OR genetic testing confirming full or partial loss of the LAL gene; 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Member's current weight provided for dosing verification.

inv-08: Lamzede (velmanase alfa)

Covered when ALL of the following are met

Lamzede: 1) Diagnosis of alpha-mannosidosis; 2) Member is > 3 years of age; 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Copy of genetic testing confirming MAN2B1 mutation; 5) Baseline measurements including serum oligosaccharides and ONE motor function test (forced vital capacity, 3-minute stair climb test, or 6-minute walk test); 6) Member's current weight provided for dosing verification.

inv-09: Lumizyme (alglucosidase alfa) and Nexviazyme (avalglucosidase alfa)

Covered when ALL of the following per agent are met

Lumizyme: 1) Diagnosis of Pompe disease; 2) Diagnostic confirmation via GAA assay (cultured skin fibroblasts, lymphocyte testing, or blood spot assay) or genetic testing confirming GAA mutation; 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Member's current weight provided for dosing verification;

Lumizyme and Nexviazyme should not be used concurrently.

Nexviazyme: 1) Diagnosis of late-onset Pompe disease with diagnostic confirmation via GAA assay (cultured skin fibroblasts, lymphocyte testing, or blood spot assay) or genetic testing confirming GAA mutation; 2) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 3) Member is > one year of age; 4) Member's current weight provided for dosing verification; 5) If reviewed under the pharmacy benefit for members weighing >=30 kg, documentation of contraindication to Lumizyme is required;

Lumizyme and Nexviazyme should not be used concurrently.

inv-10: Mepsevii (vestronidase alfa)

Covered when ALL of the following are met

Mepsevii: 1) Diagnosis of Mucopolysaccharidosis VII (MPS VII, Sly syndrome); 2) Results from genetic testing showing mutations in the beta-glucuronidase (GUSB) gene; 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Member's current weight provided for dosing verification.

inv-11: Naglazyme (galsulfase)

Covered when ALL of the following are met

Naglazyme: 1) Diagnosis of Mucopolysaccharidosis VI (MPS VI); 2) Results from an enzyme assay demonstrating reduced arylsulfatase B (ASB) activity in leukocytes or fibroblasts with elevated urine glycosaminoglycan (GAG) levels; 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Member's current weight provided for dosing verification.

inv-12: Nulibry (fosdenopterin)

Covered when ALL of the following are met

Nulibry: 1) Diagnosis of molybdenum cofactor deficiency (MoCD) Type A confirmed by genetic testing; 2) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 3) Appropriate dosing requested; 4) Member's current weight provided for dosing verification.

Reauthorization requires documentation of positive response to therapy or clinical rationale for continued use.

inv-13: Palynziq (pegvaliase-pqpz)

Covered when ALL of the following are met

Palynziq: 1) Diagnosis of phenylketonuria (PKU); 2) Member is > 18 years of age; 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Blood phenylalanine concentration > 600 micromol/L; 5) Medication will be used in conjunction with a phenylalanine-restricted diet; 6) If reviewed under the pharmacy benefit: physician attestation of inadequate response, adverse reaction, or contraindication to sapropterin.

inv-14: Revcovi (elapegademase-lvlr)

Covered when ALL of the following are met

Revcovi: 1) Diagnosis of ADA-SCID; 2) Laboratory documentation of ONE of the specified ADA-SCID biochemical/immunologic findings (e.g., absent ADA activity in lysed erythrocytes; elevated adenosine/deoxyadenosine; marked increase in dATP in erythrocyte lysates; absent or extremely low S-adenosylhomocysteine hydrolase; decreased ATP in red blood cells; severe T-cell deficiency); 3) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 4) Member's current weight provided for dosing verification; 5) Absent thymic shadow on chest radiograph.

inv-15: Ryplazim (plasminogen, human)

Covered when ALL of the following are met

Ryplazim: 1) Diagnosis of plasminogen deficiency (PLGD) type 1; 2) History of lesions and symptoms consistent with PLGD type 1 (e.g., ligneous conjunctivitis or gingivitis, vision abnormalities, respiratory distress/obstruction, abnormal wound healing); 3) Baseline plasminogen activity level <45% or genetic testing showing PLG mutations; 4) ONE of: plasminogen antigen level <9 mg/dL OR requested dose is <6.6 mg/kg every 2-4 days; 5) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided.

Baseline plasminogen activity >=45% or plasminogen antigen >=9 mg/dL may fail to meet numeric thresholds for approval.

inv-16: Revcovi (elapegademase-Ivlr) initial therapy

Covered when ALL of the following are met

Revcovi initial criteria: 1) Diagnosis of ADA-SCID established by laboratory evidence as listed in the policy; 2) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 3) Absent thymic shadow on chest radiograph; 4) Current member weight documented for dosing.

Laboratory list includes absent ADA activity; elevated adenosine/deoxyadenosine; increased dATP; absent S-adenosylhomocysteine hydrolase; decreased ATP; severe T-cell deficiency.

inv-17: Ryplazim (plasminogen, human-tvmh) initial therapy

Covered when ALL of the following are met

Ryplazim initial criteria: 1) Diagnosis of PLGD type 1; 2) History of lesions and symptoms consistent with PLGD type 1; 3) Baseline plasminogen activity level <45%; 4) Genetic testing showing PLG mutations; 5) Either plasminogen antigen <9 mg/dL OR requested dose <6.6 mg/kg every 2-4 days.

inv-18: Vimizim (elosulfase alfa) initial therapy

Covered when ALL of the following are met

Vimizim initial criteria: 1) Diagnosis of Mucopolysaccharidosis IVA (Morquio A syndrome); 2) Member is >= 2 years of age; 3) Enzyme assay demonstrating reduced N-acetylgalactosamine-6-sulfatase activity in blood and/or skin cells; 4) Prescriber is a specialist in genetic or metabolic diseases or consultation notes from a specialist are provided; 5) Member's current weight provided for dosing verification.

inv-19: Xenpozyme (olipudase alfa-rpcp) initial therapy

Covered when ALL of the following are met

Xenpozyme initial criteria: 1) Diagnosis of non-CNS manifestations of ASMD type B or ASMD type A/B; 2) Prescriber is a specialist (e.g., medical geneticist or specialist familiar with lysosomal storage disorders) or consultation notes from a specialist are provided; 3) ONE of: DLco < 70% of predicted OR (for members >=18 years spleen volume > 6 MN; for members < 18 years spleen volume > 5 MN); 4) BOTH: member does NOT have acute or rapidly progressive neurologic abnormalities AND member does NOT require invasive ventilatory support AND member does NOT require noninvasive ventilatory support while awake for > 12 hours/day; 5) Member's current weight documented; 6) Appropriate dosing requested.

inv-20: Lamzede (continuation)

Lamzede continuation/reauthorization criteria

Lamzede reauthorization criteria: Prescriber must provide documentation of ONE of the following: 1) Current tests (within the past 3 months) documenting positive response to therapy for ALL of the following tests: serum oligosaccharides, forced vital capacity, and ONE motor function test (3-minute stair climb OR 6-minute walk test); OR 2) Medical necessity for continuing therapy (e.g., disease stabilization or reduction in expected motor decline).

Reauthorization for Ryplazim and Nulibry requires physician documentation of positive response to therapy or clinical rationale for continued use; Xenpozyme reauthorization requires updated weight and improvement in DLco and spleen volume.

For treatment of Pompe disease, Lumizyme (alglucosidase alfa) and Nexviazyme (avalglucosidase alfa) are distinct enzyme replacement therapy options and should not be used concurrently. This prohibition is stated in the agent-specific coverage criteria for both Lumizyme and Nexviazyme and applies regardless of benefit channel (medical or pharmacy).

Initial authorization durations vary by agent: Ryplazim: 24 weeks; Lamzede, Nulibry, Palynziq, and Xenpozyme: 6 months; and all other agents: 1 year. Standard reauthorizations for most agents are 1 year. These timeframes are the default limits applied at initial approval and reauthorization; individual requests remain subject to required documentation and agent-specific criteria.

Members who are already stable on Nulibry (fosdenopterin) must meet both the initial and the reauthorization criteria to continue receiving coverage. Failure to provide the documentation required by either the initial approval rules or the reauthorization criteria may result in denial of continued therapy.

Numeric and Age Thresholds Used in Criteria

Baseline plasminogen activity level — <45%

Baseline plasminogen activity level< 45%

ContextRequired baseline threshold for Ryplazim (plasminogen, human-tvmh) initial approval

Supporting evidenceDocumented in Ryplazim initial criteria listing clinical and laboratory requirements

Plasminogen antigen level — <9 mg/dL

Plasminogen antigen level< 9 mg/dL

ContextOne of the numeric criteria options for Ryplazim initial approval

Usage

Authorization Process, Documentation & Prescriber Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for all listed enzyme and metabolic therapies under this policy. Requests for members new to the plan who are currently receiving the requested medication may be reviewed case‑by‑case; continued coverage is not guaranteed unless the request meets the criteria below.

All listed products require Prior Authorization.
New‑to‑plan members on active treatment: may require case‑by‑case review and supporting documentation; absence of required documentation or failure to meet clinical criteria may result in denial.

Documentation Required

Documentation Required (Diagnosis, Specialist & Weight)

Authorization requests must include documentation that confirms diagnosis and supports medical necessity, including diagnostic testing and evidence of specialist involvement. Provide current clinical data used for dosing and selection of the requested agent.

Diagnosis confirmation: genetic testing results or enzyme assay as specified by the agent.

Clinical Background

Lysosomal storage disorders are inherited conditions caused by deficiency or absence of specific lysosomal enzymes, leading to accumulation of undegraded substrates and multisystem disease. Enzyme replacement therapies (ERTs) and related agents provide exogenous enzyme activity to reduce substrate storage and address disease manifestations; coverage of these agents requires documented diagnosis confirmation, appropriate laboratory or genetic testing, specialist prescriber involvement or consultation notes, and dosing verification by current member weight.

Diagnostic and Condition Definitions

Lysosomal storage disorders — definition/key features

DefinitionInherited conditions caused by deficiency or absence of specific lysosomal enzymes resulting in accumulation of undegraded compounds and multisystem disease.

Key featuresProgressive organ dysfunction due to substrate accumulation; many are treated with enzyme replacement therapies (ERT).

ExamplesGaucher disease, Fabry disease, mucopolysaccharidoses, Pompe disease

ADA-SCID diagnostic laboratory criteria

Diagnostic laboratory criteria (ADA-SCID)Absent ADA enzymatic activity in lysed erythrocytes; elevated adenosine and deoxyadenosine in urine/plasma; marked increase in dATP in erythrocyte lysates; absent or very low S-adenosylhomocysteine hydrolase; decreased ATP in red blood cells; severe T cell deficiency with lymphopenia and poor T-cell responses.

Context

OpenPayer

Enzyme and Metabolic Disorder Therapies — Prior Authorization and Coverage Criteria

Agent-specific Coverage Criteria

Numeric and Age Thresholds Used in Criteria

Authorization Process, Documentation & Prescriber Requirements

Clinical Background

Diagnostic and Condition Definitions