CurrentHealth NetPolicy CP PHAR.328

Clinical Policy: Asfotase Alfa (Strensiq)

Policy governs medical necessity and prior authorization criteria for asfotase alfa (Strensiq) for perinatal/infantile- and juvenile-onset hypophosphatasia across commercial, HIM and Medicaid lines of business.

Policy Summary

PayerHealth Net

PolicyAsfotase Alfa (Strensiq) clinical policy

Policy CodePolicy CP PHAR.328

Change TypeNo material change

Effective DateMar 1, 2024

Next Review DateNov 24, 2024

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) supporting that the member has met all approval criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Perinatal: 9 mg/kg/wkmaximum dosing

Juvenile: 6 mg/kg/wkdose

6–12 moauth length

Boxed warningsafety

J3490, C9399billing codes

Coverage Criteria

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Initial Therapy

Initial therapy covered when ALL of the following are met:

Diagnosis of perinatal/infantile- or juvenile-onset HPP: Age of onset < 18 years with molecular genetic testing documenting a tissue non-specific alkaline phosphatase (ALPL) gene mutation.

Clinical manifestations: History of at least one HPP clinical manifestation such as vitamin B6-dependent seizures; nephrocalcinosis with hypercalcemia/hypercalciuria; failure to thrive/growth failure/short stature; low bone mineral density with unexplained fractures; alveolar bone loss with premature loss of deciduous teeth; or skeletal abnormalities (e.g., craniosynostosis with increased intracranial pressure, rachitic chest deformity with respiratory compromise, limb deformity, compromised exercise capacity, delayed walking/gait abnormality).

Prescriber and dosing requirements: Prescribed by or in consultation with an endocrinologist; dosing must not exceed 9 mg/kg/week for perinatal/infantile-onset HPP and 6 mg/kg/week for juvenile-onset HPP.

Dose may be administered as 3 mg/kg SC three times per week or equivalent as specified in dosing guidance.

Continuation Therapy

Continuation therapy covered when:

Eligibility for continuation: Member is currently receiving the medication via the benefit or has previously met initial approval criteria; OR member is covered under continuity-of-care regulations for their state/product.

Clinical response requirement: Member demonstrates a positive clinical response to therapy, evidenced by improvement in one or more of: respiratory function; height velocity; skeletal manifestations (bone mineralization, bone formation/remodeling, fracture healing, correction of deformity); or motor function/mobility/gait.

If request is for a dose increase, the new dose must not exceed 9 mg/kg/week for perinatal/infantile-onset or 6 mg/kg/week for juvenile-onset.

Requests for indications that are not FDA-approved and are not specifically addressed in this policy are excluded unless the provider supplies adequate documentation of efficacy and safety in accordance with the applicable off‑label use policies (for example, CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, or CP.PMN.53 for Medicaid) or other evidence of coverage documents.

When there is a conflict between this clinical policy and state Medicaid coverage provisions, the state Medicaid requirements take precedence. Providers must follow applicable state and federal requirements and the member’s evidence of coverage or other plan documents when those documents differ from this policy.

Off‑label use requests for indications not FDA‑approved and not addressed in this policy may be denied if the submission does not include sufficient documentation of efficacy and safety per the payer’s off‑label use policies. Providers should follow the referenced off‑label policies and supply supporting clinical evidence to avoid denial.

Initial Therapy

Initial approval criteria and dosing limits

Diagnostic and clinical requirements: Must have diagnosis of perinatal/infantile- or juvenile-onset HPP supported by genetic testing or laboratory confirmation and at least one clinical manifestation consistent with HPP (see policy clinical manifestations).

Prescriber requirement: Prescribed by or in consultation with an endocrinologist.

Dosing limits: Dosing must not exceed 9 mg/kg/week for perinatal/infantile-onset HPP and 6 mg/kg/week for juvenile-onset HPP.

Perinatal/infantile-onset dosing may be administered as up to 3 mg/kg SC three times per week (up to 9 mg/kg/week); juvenile-onset dosing may be administered as 2 mg/kg SC three times per week (6 mg/kg/week) or equivalent regimens noted in dosing guidance.

Continuation / Renewal Criteria

Continuation Therapy

Requirements for renewal/continuation

Continuation eligibility: Member is currently receiving the medication or previously met initial approval criteria, or continuity-of-care provisions apply.

Evidence of clinical benefit: Documented positive response to therapy demonstrated by improvement in respiratory function, height velocity, skeletal manifestations (bone mineralization, fracture healing, deformity improvement), or motor function/mobility/gait on the re-authorization request.

Dose change condition: If a dose increase is requested, the new dose must not exceed the maximums: 9 mg/kg/week for perinatal/infantile-onset or 6 mg/kg/week for juvenile-onset.

Coding and Dosing

HCPCS Codes referencedHCPCS

J3490	Unclassified drugs or biologicals (listed in policy)
C9399	Unclassified drugs or biologicals (listed in policy)

Referenced HCPCS CodesHCPCS

J3490	Unclassified drugs or biologicals (HCPCS) - referenced
C9399	Unclassified drugs or biologicals (HCPCS) - referenced

inv-08: Maximum weekly dose — perinatal/infantile-onset and juvenile-onset dosing limits

Perinatal/infantile-onset maximumUp to 9 mg/kg per week (maximum dose) — may be administered as 3 mg/kg SC three times per week or equivalent; dose may be increased for lack of efficacy up to 9 mg/kg/week.

Perinatal/infantile-onset typical regimenDosing regimen described as 6 mg/kg SC per week (various schedules permitted); maximum 9 mg/kg/week.

Juvenile-onset maximumMaximum dose 6 mg/kg per week — commonly administered as 2 mg/kg three times per week or equivalent.

inv-09: Approval duration (historical) — 6 months or to member's renewal date

Medicaid/HIM (historical)Medicaid/HIM historically referenced ~6 months to 12 months depending on program; continuation guidance notes Medicaid/HIM typically 12 months for renewals.

Policy revision note4Q2020 annual review updated commercial approval duration; later reviews (4Q2021–4Q2024) noted no significant changes to duration wording.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (such as office chart notes, laboratory results, genetic testing reports, and other clinical information) supporting the diagnosis and that the member meets all approval criteria. Requests should include prescribing provider specialty and rationale for therapy.

Include molecular genetic testing results (e.g., ALPL gene) when applicable
Include baseline laboratory indices (e.g., low serum alkaline phosphatase, elevated substrates such as pyridoxal 5'-phosphate or urinary inorganic pyrophosphate)
Provide clinical manifestations supporting the diagnosis (seizures, nephrocalcinosis, failure to thrive, skeletal abnormalities, dental findings, etc.)

Note

Provider Guidance

Providers should follow this clinical policy as guidance for coverage determinations but must exercise their professional medical judgment. The clinical policy does not replace provider decision-making; supporting documentation must be submitted to demonstrate medical necessity.

Clinical policy is a guideline — individualized treatment decisions remain the responsibility of the treating provider
Submit documentation consistent with medical necessity to support approval requests

Note

Formulary / Off‑Label Routing

For requests for uses that are off‑label or for drugs not on the formulary/PDL, follow the applicable Health Net non‑formulary or off‑label use policies for the member's line of business. Requests for non‑FDA approved indications may be denied without sufficient off‑label documentation per the referenced policies.

For formulary drugs: refer to no coverage criteria policies — Commercial: CP.CPA.190; Health Insurance Marketplace: HIM.PA.33; Medicaid: CP.PMN.255
For non‑formulary drugs: refer to non‑formulary policies — Commercial: CP.CPA.190; Health Insurance Marketplace: HIM.PA.103; Medicaid: CP.PMN.16
For off‑label use documentation requirements: Commercial: CP.CPA.09; Health Insurance Marketplace: HIM.PA.154; Medicaid: CP.PMN.53

Billing Rule

Coding Inclusion/Exclusion Disclaimer

Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up‑to‑date professional coding guidance when submitting claims for reimbursement.

Inclusion or exclusion of codes does not guarantee coverage
Verify coding with current coding manuals and payer billing guidance prior to claim submission

Denial Risk

Non‑Approved Indications

Requests for indications not FDA‑approved and not addressed in this policy require adequate off‑label documentation of efficacy and safety per the applicable off‑label use policy; lacking sufficient documentation, such requests may be denied.

Non‑approved indications may be denied without sufficient off‑label documentation (see CP.CPA.09 / HIM.PA.154 / CP.PMN.53)

Documentation Required

Required Clinical Documentation

Provider must submit chart notes, lab results, genetic testing, and other clinical information to support that the member meets the stated criteria for approval.

Office/chart notes documenting clinical manifestations and functional status
Relevant laboratory data and genetic testing reports
Treatment history and prescribing provider specialty/consultation notes

Formulary / Step Therapy Routing

Scenario	Required routing / referenced policies
Drug is on the formulary (commercial or health insurance marketplace) or on the PDL (Medicaid)	Follow the no‑coverage / formulary criteria policy for the relevant line of business: CP.CPA.190 (commercial), HIM.PA.33 (health insurance marketplace), or CP.PMN.255 (Medicaid). If the drug recently had a label change not reflected in this policy, follow the referenced policy guidance as applicable.
Drug is NOT on the formulary (commercial or health insurance marketplace) or NOT on the PDL (Medicaid)	Follow the non‑formulary policy for the relevant line of business: CP.CPA.190 (commercial), HIM.PA.103 (health insurance marketplace), or CP.PMN.16 (Medicaid).
Requested use (diagnosis, age, or dosing regimen) is not listed in this policy and criterion above does not apply	Refer to the off‑label use policy for the relevant line of business: CP.CPA.09 (commercial), HIM.PA.154 (health insurance marketplace), or CP.PMN.53 (Medicaid).

Background

Hypophosphatasia (HPP) is a rare metabolic bone disease caused by loss‑of‑function mutations in the ALPL gene resulting in deficient tissue nonspecific alkaline phosphatase activity and accumulation of its substrates. The resulting biochemical abnormalities (for example, low serum alkaline phosphatase with elevated substrates such as pyridoxal 5'-phosphate and inorganic pyrophosphate) produce clinical manifestations including impaired bone mineralization, fractures, growth failure, respiratory compromise in severe forms, tooth loss, and neurologic features such as vitamin B6‑dependent seizures. Asfotase alfa (Strensiq) is a targeted enzyme replacement therapy — a tissue nonspecific alkaline phosphatase — approved to treat perinatal/infantile‑ and juvenile‑onset HPP to improve bone mineralization and related clinical outcomes.

Definitions and Purpose

inv-19: HPP / Asfotase alfa — drug indication and brief description

Drug and brandAsfotase alfa (Strensiq)

IndicationTreatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).

Mechanism / descriptionRecombinant tissue nonspecific alkaline phosphatase (enzyme replacement) used to improve bone mineralization and HPP-related manifestations; dosing regimens and maximum weekly doses differ by age of onset.

inv-20: Clinical policy purpose — guidance purpose and disclaimer

Primary purposeProvide guidance to assist in making coverage decisions and administering benefits; not medical advice and not a guarantee of payment.

Scope of useIntended as a guideline for medical necessity determinations; coverage decisions subject to evidence of coverage, state/federal requirements, and Health Plan administrative policies.

DisclaimerThe Health Plan makes no representations or accepts liability for external information used in developing this clinical policy; this policy does not constitute a contract.

OpenPayer

Clinical Policy: Asfotase Alfa (Strensiq)

Coverage Criteria

Initial Therapy

Continuation / Renewal Criteria

Coding and Dosing

Provider Actions and Requirements

Site of Care

Formulary / Step Therapy Routing

Background

Definitions and Purpose