Prior authorization required

Submit prior authorization for all ERT initial and continuation requests with the specified documentation listed under “Required Documentation” to initiate review; approvals are contingent on meeting the product-specific diagnostic and response documentation requirements.

• Initial requests: submit the agent-specific diagnostic confirmation (enzyme assay and/or genetic testing) as listed for the product (see product entries).
• Continuation requests: submit chart notes, lab results or other records documenting clinical response, stabilization, or slowing of disease progression as specified per product.

Prior authorization and approval durations

Authorizations are issued for limited durations per product: many ERT approvals are for 12 months, Adzynma example is 6 months, and Nulibry initial approval examples are 3 months; renewal requires submission of continuation documentation showing clinical benefit.

• Examples: Brineura, Fabrazyme, Loargys, Lumizyme, Nexviazyme and many others—approval is for 12 months.
• Nulibry initial pathway examples reference a 3‑month initial approval period.
• Adzynma approval example referenced as a 6‑month duration in the brief.

Time-limited approvals — submit continuation evidence

Prior authorization approvals are time-limited and continuation requests must include the product-specific evidence of benefit (e.g., chart notes, lab values, functional test results) per the continuation criteria to obtain renewal.

• Initial approvals are often 3–12 months depending on the product; continuation approvals generally require documentation of maintained or improved clinical status.
• Continuation evidence examples include Motor/Language CLN2 scores for Brineura, pre-dose plasma arginine for Loargys, and functional/respiratory measures for Pompe therapies.

Prior authorization required for ERTs — include diagnosis and prior therapy info

Obtain prior authorization for all enzyme replacement therapies; initial requests must include the product-specific diagnostic confirmation (enzyme assay or genetic testing) and continuation requests must document response as specified.

• Example: Pombiliti/Opfolda combination requires documentation of prior ERT exposure and that the patient is not improving on current ERT.
• Ensure the diagnostic and response documentation listed under each product (e.g., ADAMTS13 assay for Adzynma; acid alpha‑glucosidase assay for Pompe agents) is attached to the PA request.

Prior authorization required for listed drug/billing codes

Use the listed HCPCS/J-codes when submitting authorizations and claims; prior authorization is required for therapies reported with the codes in the policy and claims should use currently effective codes.

• Report the product with its current HCPCS/J-code (e.g., J0219 for Nexviazyme effective 4/1/2022; J0218 for Xenpozyme effective 4/1/2023).
• Do not submit claims with cancelled codes (see code list) — use the effective replacement code when required.

Policy intends to steer utilization to cost‑effective agents

The policy explicitly aims to steer utilization to the most cost‑effective medication within the therapeutic class; document rationale if requesting a higher‑cost or less‑preferred agent.

• Provide clinical justification when requesting newer or combination therapies versus established ERTs to support medical necessity decisions.

Combination therapy required for Opfolda + Pombiliti

For late‑onset Pompe disease, Opfolda (miglustat) and Pombiliti (cipaglucosidase alfa) must be prescribed and continued in combination per the indication; prior ERT exposure and inadequate response to current ERT must be documented for eligibility.

• Initial and continuation criteria require the medication be taken in combination (Opfolda with Pombiliti).
• Document that the adult patient (≥18 years) weighs ≥40 kg and is not improving on current ERT (e.g., Lumizyme, Nexviazyme).

Combination/previous therapy conditions — product‑specific

Do not combine certain therapies per policy rules: Elfabrio and Fabrazyme must not be used in combination with Galafold; Loargys requires prior inadequate response/intolerance/contraindication to nitrogen scavenger therapy and documentation of that history.

• Elfabrio and Fabrazyme: include documentation that therapy will not be used in combination with Galafold.
• Loargys: submit evidence of inadequate response, intolerable adverse effect, or contraindication to nitrogen scavenger therapy (e.g., sodium phenylbutyrate, glycerol phenylbutyrate).

Document prior ERT exposure and inadequate response for Pompe combination therapy

For therapies approved only in ERT‑experienced patients (Pombiliti + Opfolda), document prior ERT exposure and that the member is not improving on their current ERT; continuation also requires ongoing combination use.

• The Pombiliti+Opfolda approval is based largely on ERT‑experienced populations; include prior ERT treatment history and clinical measures demonstrating inadequate response.
• Continuation criteria for Pombiliti require the medication continue to be taken in combination with Opfolda and evidence of response.

Prior ERT exposure and patient eligibility required for Pombiliti + Opfolda

Approval of Pombiliti in combination with Opfolda is limited to adult late‑onset Pompe patients (≥40 kg) who are not improving on their current ERT; also note contraindication in pregnancy and boxed warnings for severe hypersensitivity and cardiorespiratory failure.

• Include weight (≥40 kg), adult age (≥18 years), documentation of current ERT and evidence of inadequate clinical response.
• Be aware the combination carries boxed warnings and is contraindicated in pregnancy—document pregnancy status where applicable.

Step therapy not specified for some therapies (e.g., Nulibry)

No formal step‑therapy cascade is defined in the policy for Nulibry or other therapies; if requesting therapies without explicit step requirements, include full diagnostic and clinical justification per the product criteria.

• For Nulibry and several rare‑disease therapies, the policy does not specify mandatory prior agents—rely on diagnostic confirmation and clinical indications to support PA requests.

Required documentation overview — initial and continuation

Attach the specific documentation categories listed under “Required Documentation” for the product: initial requests require diagnostic confirmation (enzyme assay and/or genetic testing) and continuation requests require chart notes or labs documenting clinical benefit, stabilization, or slowing of progression.

• Verify the product‑specific required items (see product entries I–XIX) and include them with the PA submission to avoid delays.
• Prescriber specialty requirements may apply—some products must be prescribed by or in consultation with a metabolic disease or lysosomal storage disorder specialist.

Adzynma (ADAMTS13) — documentation required

For Adzynma initial requests, submit ADAMTS13 enzyme assay and ADAMTS13 genetic testing results; continuation requests must include medical records documenting therapeutic response (e.g., reduction/maintenance of TTP events, platelet count increase, decreased LDH).

• Initial: ADAMTS13 enzyme assay and genetic testing confirming biallelic ADAMTS13 mutations and activity <10% at diagnosis.
• Continuation: chart notes or lab reports documenting response measures (TTP event frequency, platelet counts, LDH).

Aldurazyme — documentation required

For Aldurazyme initial requests, include alpha‑L‑iduronidase enzyme assay and/or genetic testing supporting MPS I diagnosis; continuation requires chart notes documenting improvement, stabilization, or slowing of disease progression.

• Initial: enzyme assay and/or genetic testing confirming MPS I.
• Continuation: clinical documentation of response (improvement, stabilization, or slowed progression).

Brineura — documentation and administration requirements

For Brineura initial requests, submit TPP1 enzyme assay or genetic testing confirming CLN2; continuation requests must include chart notes documenting clinically positive response (improvement, stabilization, or slowed loss of ambulation).

• Initial: TPP1 enzyme assay or genetic testing and documentation that Brineura will be administered by/under direction of a physician experienced in intraventricular administration.
• Continuation: documentation showing no loss or slowed loss of ambulation compared with baseline motor domain scores.

Elaprase — documentation required

For Elaprase initial requests, include iduronate 2‑sulfatase enzyme assay or genetic testing supporting MPS II diagnosis; continuation requires chart notes documenting clinically positive response.

• Initial: enzyme assay or genetic testing supporting diagnosis.
• Continuation: chart notes documenting improvement, stabilization, or slowing of disease progression.

Elfabrio — documentation required

For Elfabrio initial requests, submit alpha‑galactosidase enzyme assay or genetic testing supporting Fabry disease diagnosis (parent documentation if obligate carrier); continuation requires labs or chart notes documenting response (e.g., reduction in GL‑3/Gb3, renal improvement, pain reduction).

• Initial: enzyme assay or genetic testing (or parent documentation for obligate carriers).
• Continuation: lab results or chart notes showing biochemical or clinical improvement (GL‑3/Gb3 reductions, renal/pain measures).

Fabrazyme — documentation required

For Fabrazyme initial requests, include alpha‑galactosidase enzyme assay or genetic testing supporting Fabry diagnosis (parent documentation if obligate carrier); continuation requires labs or chart notes documenting response (e.g., reduction in GL‑3/Gb3, renal improvement, pain reduction).

• Initial: enzyme assay or genetic testing (or parent documentation for obligate carriers).
• Continuation: evidence of biochemical or clinical response as specified.

Kanuma — documentation and ALT requirement

For Kanuma initial requests, submit lysosomal acid lipase enzyme assay or genetic testing; continuation requires labs or chart notes documenting response (e.g., growth z‑scores, lipids, ALT) and ALT ≥1.5x ULN on two measurements is an approval criterion.

• Initial: enzyme assay or genetic testing confirming LAL deficiency.
• Continuation: objective measures showing response (growth, lipid profile, ALT).
• Approval criterion: ALT ≥1.5 × ULN on two consecutive measurements at least one week apart.

Lamzede — documentation and dosing limit

For Lamzede initial requests, submit alpha‑mannosidase enzyme assay or genetic testing and documentation that the member has no neurological (CNS) manifestations; continuation requires documentation of response using 3MSCT, 6MWT, FVC % predicted, or oligosaccharide reductions. Also ensure dose does not exceed 1 mg/kg once weekly.

• Initial: enzyme assay or genetic testing and chart notes documenting absence of CNS disease.
• Continuation: functional test results (3MSCT, 6MWT, FVC % predicted) or oligosaccharide reduction from baseline.
• Dose limit: ≤ 1 mg/kg once weekly.

Loargys — documentation and monitoring

For Loargys initial requests, submit diagnostic assay/genetic results, baseline plasma arginine ≥250 µmol/L, and documentation of inadequate response/intolerance/contraindication to nitrogen scavenger therapy; continuation requests require pre‑dose plasma arginine monitoring.

• Initial: enzyme/ genetic confirmation and baseline plasma arginine ≥250 micromol/L.
• Document prior inadequate response or intolerance to nitrogen scavengers (e.g., sodium phenylbutyrate, glycerol phenylbutyrate).
• Continuation: pre‑dose plasma arginine lab results per manufacturer guidance; dose must not exceed 0.2 mg/kg once weekly.

Lumizyme — documentation and safety monitoring

For Lumizyme initial requests, include acid alpha‑glucosidase enzyme assay or genetic testing supporting Pompe diagnosis; continuation requests must include chart notes documenting positive response (motor, walking, cardiorespiratory function, LVMI, survival delay). Note the FDA black box warning for severe adverse reactions.

• Initial: enzyme assay or genetic testing confirming Pompe disease.
• Continuation: clinical documentation of benefit (motor function, 6MWT, respiratory function, LVMI, survival).
• Safety: Lumizyme has a boxed warning for anaphylaxis, hypersensitivity, immune‑mediated reactions, and acute respiratory failure.

Nexviazyme — documentation and dosing

For Nexviazyme initial requests, submit acid alpha‑glucosidase enzyme assay or genetic testing supporting Pompe diagnosis and patient age ≥1 year; continuation requests require chart notes documenting clinical response (motor, walking, respiratory function, muscle strength).

• Initial: enzyme assay or genetic testing and age ≥1 year.
• Continuation: documentation of clinical benefit (e.g., FVC % predicted, 6MWT, muscle strength).
• Dosing: Nexviazyme IV q2w at 20 mg/kg for ≤30 kg or 40 mg/kg for >30 kg.

Required diagnostic and response documentation — general

Required diagnostic and response documentation: initial requests must include the agent‑specific enzyme assay or genetic testing; continuation requests must include chart notes or labs documenting clinical improvement, stabilization, or slowing of progression as specified per product.

• Provide the specified diagnostic confirmation for the requested product.
• For continuation, provide objective measures of response appropriate to the disease and product (examples vary by agent).

Prescriber specialty requirement — include specialist consultation when required

Some medications must be prescribed by or in consultation with a specialist experienced in metabolic disease or lysosomal storage disorders; verify prescriber specialty and include consultation documentation when required.

• Products requiring specialist prescribing/consultation include Aldurazyme, Elfabrio, Elaprase, Fabrazyme, Kanuma, Loargys, Lumizyme, Mepsevii, Naglazyme, Nexviazyme, Nulibry, Opfolda, Pombiliti, and Vimizim.

Diagnostic confirmation and baseline clinical documentation required

Confirm diagnosis by appropriate testing (enzyme assay demonstrating deficient enzyme activity or genetic testing) and document baseline clinical signs/symptoms or functional measures as specified for the product to support medical necessity.

• Examples: CLN2 baseline motor domain score for Brineura; baseline plasma arginine and clinical history for Loargys; baseline respiratory and motor measures for Pompe therapies.

Diagnostic and baseline functional documentation — trial measures

Provide baseline functional scores or trial‑relevant measures used in pivotal studies when available (e.g., CLN2 Motor and Language scores for Brineura; survival/genotype matching and urine SSC for Nulibry) to support medical necessity.

• Include CLN2 Clinical Rating Scale Motor scores at baseline for Brineura patients to demonstrate ambulatory status.
• For Nulibry, include genetic confirmation and baseline urine SSC and survival context where applicable.

Clinical and diagnostic documentation for rare disease therapies

For rare disease therapies, include genetic confirmation of diagnosis and relevant baseline/follow‑up measures used in supporting trials (e.g., genetic MOSC1 confirmation for Nulibry, urine SSC levels, lung function, organ volumes, platelet counts).

• Nulibry: genetic testing documenting MOSC1 mutation and measures such as urinary SSC and uric acid.
• Xenpozyme: baseline/ follow‑up lung function, spleen/liver volumes, platelet counts, and growth metrics.

Benefit applicability and verification required — may trigger denial

Verify member benefit and contract applicability before submitting PA; benefit exclusions, limitations, or exceptions may prevent coverage even if medical criteria are met.

• Benefits are determined by the member's contract and Wellmark determines medical necessity only if the benefit exists and no contract exclusions apply.
• Confirm FEP applicability and any contract‑specific exclusions prior to PA submission.

Missing diagnostic documentation will risk denial

Failure to provide the required diagnostic confirmation (enzyme assay or genetic testing) for initial requests may result in denial for the requested therapy.

• Initial PA must include the specific enzyme assay or genetic testing results cited in the product entry (e.g., ADAMTS13 assay for Adzynma; acid alpha‑glucosidase assay for Pompe agents).
• Omitting these documents is a common basis for denial.

Insufficient continuation documentation may lead to denial

Insufficient continuation documentation (lack of chart notes or lab evidence demonstrating clinical benefit, stabilization, or slowing of disease progression) may lead to denial of renewal requests.

• Provide objective measures of response per product (e.g., motor function, FVC, 6MWT, pre‑dose plasma arginine) when requesting continuation.
• Absence of these data can result in non‑renewal.

Failure to meet listed criteria — denial risk

Requests that do not meet the product‑specific criteria set forth in the policy (diagnostic thresholds, age/weight limits, prior therapy conditions, dosing limits) will be considered not medically necessary and may be denied.

• Examples: Loargys requires baseline plasma arginine ≥250 µmol/L and prior inadequate response to nitrogen scavengers; Lamzede dose must not exceed 1 mg/kg once weekly.
• Pombiliti+Opfolda requires adult patients ≥40 kg who are not improving on current ERT.

Safety‑triggered denial risk — monitor and document

Severe adverse reactions (anaphylaxis, hypersensitivity, immune‑mediated reactions, acute respiratory failure) associated with some ERTs (notably Lumizyme) are safety triggers that may affect authorization and require monitoring per prescribing information.

• Lumizyme prescribing information includes a boxed warning for severe reactions; document monitoring plans and clinical justification if safety concerns exist.
• Safety events may prompt denial or require additional monitoring documentation.

Safety/contraindication‑triggered denial risk for Pombiliti + Opfolda

Pombiliti plus Opfolda carries boxed warnings for severe hypersensitivity and acute cardiorespiratory failure and is contraindicated in pregnancy; these safety and contraindication issues must be documented and can affect authorization decisions.

• Document pregnancy status and contraindications; do not request authorization for pregnant members as the combination is contraindicated.
• Include monitoring and risk‑mitigation plans given boxed warnings for infusion‑associated severe hypersensitivity and cardiorespiratory risks.

Coding‑related denial risk — use current HCPCS/J‑codes

Claims or prior authorization requests lacking the appropriate, currently effective HCPCS/J‑codes or using cancelled codes may trigger billing denials or coverage issues; confirm and use the effective code from the policy’s code lists.

• Examples: use J0219 (Nexviazyme) or J0218 (Xenpozyme) as effective codes rather than cancelled codes like C9085.
• Include the correct code on the PA and claim to avoid coding‑related denials.