ModifiedPremera BluecrossPolicy N/A

Pharmacotherapy of Perinatal/Infantile and Juvenile-Onset Hypophosphatasia (HPP)

This policy governs coverage and medical necessity criteria for Strensiq (asfotase alfa) for genetically confirmed perinatal/infantile- and juvenile-onset HPP delivered through the pharmacy benefit; it applies to providers prescribing or consulting on therapy.

Policy Summary

PayerPremera Bluecross

PolicyPharmacotherapy of Perinatal/Infantile and Juvenile-Onset Hypophosphatasia (HPP)

Policy CodePolicy N/A

Change TypeMaterial revisions to coverage criteria and authorization length

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization through the pharmacy benefit with documentation of genetic confirmation, pediatric-onset (<18 years), persistently low age-adjusted ALP on ≥2 measurements, radiographic support, specialist prescribing/consultation, and dosing within policy limits.

SourceLink

POLICY UPDATE CHANGES

Updated coverage criteria for Strensiq (asfotase alfa) adding a dosage limitation and requirement that for members >40 kg the provider attests to permitting specialty pharmacy to determine vial strengths to minimize waste.

Changed reference timing from 'at time of diagnosis' to 'prior to 18 years of age' across criteria.

Updated alkaline phosphatase (ALP) requirement to show persistently low age-adjusted serum ALP on at least two separate measurements prior to 18 years of age.

Updated skeletal radiograph examples to include rickets, recurrent metatarsal stress fractures, and specified atypical fractures as atypical femoral fractures.

Updated specialist requirement to remove 'doctor that specializes in treatment of hypophosphatasia or other related disorders' and list nephrologist or rheumatologist.

Updated initial authorization length for all other reviews from 6 months to 12 months.

Added a prescriber requirement for Strensiq (asfotase alfa) coverage criteria in 2024.

Clarified that non-formulary exception review authorizations may be approved up to 12 months and that medications listed are subject to FDA dosing/administration.

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

9 mg/kg/weekperinatal/infantile HPP dose limit

6 mg/kg/weekjuvenile-onset HPP dose limit

Up to 12 monthsapproval length

12 monthsupdated standard auth length

75%anti-asfotase alfa Ab+

Coverage Criteria for Strensiq (asfotase alfa)

Initial Therapy

Strensiq may be considered medically necessary when ALL of the following are met:

Initial authorization criteria: Age of onset < 18 years AND genetic testing showing mutation in the ALPL gene AND age-adjusted serum alkaline phosphatase (ALP) persistently below the lower limit of normal (present on at least 2 separate measurements) prior to 18 years of age AND (plasma pyridoxal 5'-phosphate (PLP) greater than the upper limit of normal prior to 18 years of age OR urinary phosphoethanolamine (PEA) greater than the upper limit of normal prior to 18 years of age) AND skeletal radiographs supporting HPP prior to 18 years of age (e.g., rickets, osteomalacia, calcific periarthritis, atypical femoral fractures, recurrent metatarsal stress fractures) AND prescribed by or in consultation with an endocrinologist, geneticist, nephrologist, or rheumatologist AND dose limited to perinatal/infantile-onset HPP: 9 mg/kg per week or juvenile-onset HPP: 6 mg/kg per week

Re-authorization

Re-authorization may be approved up to 12 months when ALL of the following are met:

Re-authorization criteria: Continued documentation that drug-specific coverage criteria are met AND chart notes demonstrate the individual continues to show a positive clinical response to therapy as supported by one of the following: skeletal radiographs OR alkaline phosphatase (ALP) OR plasma pyridoxal 5'-phosphate (PLP) OR urinary phosphoethanolamine (PEA) levels

Approval period up to 12 months

Investigational / Not Medically Necessary

Not covered/Investigational: All other uses of Strensiq (asfotase alfa), including adult-onset hypophosphatasia (HPP) and other non-specified indications, are considered investigational and not medically necessary.

Strensiq is subject to FDA dosing and administration.

Updated coverage requirements (supplemental)

Key updated coverage requirements and limits (supplemental to full criteria in Part 1):

Laboratory evidence: Age-adjusted serum ALP persistently below the lower limit of normal on at least two separate measurements prior to 18 years of age.>=2 measurements

Replaces prior single-measurement requirement; applies prior to 18 years of age.

Radiographic findings: Skeletal radiograph examples supporting diagnosis include rickets, recurrent metatarsal stress fractures, and atypical femoral fractures.

Expanded examples added to criteria.

Prescriber requirement: Prescriber must meet updated specialty requirement (endocrinologist, geneticist, nephrologist, or rheumatologist); prescriber attestation may be required.

2024–2026 updates added and clarified prescriber specialty requirements.

Coverage statement: Use of Strensiq (asfotase alfa) for adult-onset hypophosphatasia (HPP) and for all other indications not specified in the policy is considered investigational. Strensiq is subject to the product's US Food and Drug Administration (FDA) dosage and administration prescribing information.

This medical policy does not apply to Medicare Advantage members.

Strensiq (asfotase alfa) is considered investigational (not medically necessary) for adult-onset HPP and for uses not explicitly specified in the policy's coverage criteria. The product must be used in accordance with FDA dosing and administration guidance when considered under approved indications.

Historically and per the policy record, all uses of asfotase alfa outside infantile- and juvenile-onset HPP have been treated as investigational. The policy history documents that when the drug was initially added to the prescription drug section it was limited to infantile- and juvenile-onset HPP and that "all other uses are considered investigational."

Coding and Approval Duration

Codingmixed

No codes listed

Historical HCPCS changesHCPCS

J3490

Previously listed HCPCS code (removed in earlier update)

Historical HCPCS changesHCPCS

J3590

Previously listed HCPCS code (added then removed in subsequent update as noted in history)

inv-12: Approval duration — Initial and re-authorization up to 12 months

Initial approval durationInitial authorization may be approved up to 12 months

Re-authorization durationRe-authorization may be approved up to 12 months when drug-specific criteria are met and clinical response documented

Approval period applicabilityStandard approvals and non-formulary exception reviews may be issued for up to 12 months

inv-13: Weight-based specialty pharmacy attestation threshold — Members > 40 kg provider attestation for vial-strength determination to minimize waste

Weight thresholdApplies to members weighing more than 40 kg

Provider attestation requirement

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization required through the pharmacy benefit. Approvals may be granted for up to 12 months for initial authorization and reauthorization when drug-specific coverage criteria are met and documentation demonstrates ongoing clinical benefit.

Prior authorization required through the pharmacy benefit
Approval length: up to 12 months for initial and reauthorization
Non-formulary exception requests may be considered for up to 12 months

Step Therapy

Step Therapy / Dosing

No step therapy or alternative drug sequencing requirements are specified in this policy. Dosing must follow the FDA product labeling and the policy dose limits for perinatal/infantile-onset and juvenile-onset HPP.

No step therapy requirements specified
Dose must follow FDA labeling and policy dose limits

Definitions and Diagnostic Criteria

inv-23: Perinatal/infantile- and juvenile-onset HPP — Forms with clinical onset before 18 years; infantile onset before 6 months, juvenile between 6 months and 18 years

DefinitionPerinatal/infantile- and juvenile-onset HPP are forms with clinical onset before 18 years of age

Infantile-onsetOnset before 6 months of age

Juvenile/childhood-onsetOnset between 6 months and 18 years of age

inv-24: Persistently low alkaline phosphatase (ALP) — Age-adjusted serum ALP below lower limit of normal on at least two separate measurements prior to 18 years of age

Persistently low ALP — core requirementAge-adjusted serum ALP levels persistently below the lower limit of normal on at least two separate measurements prior to 18 years of age

Timing

Background and Context

Hypophosphatasia (HPP) is a rare, inherited deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) that impairs bone mineralization and produces a spectrum of clinical severity from perinatal lethal disease to milder adult presentations. Diagnosis is based on clinical features and supportive laboratory and radiographic findings, typically including persistently low age‑adjusted serum alkaline phosphatase (ALP) and elevated substrates such as plasma pyridoxal 5'-phosphate (PLP) or urinary phosphoethanolamine (PEA), with characteristic skeletal radiographic abnormalities.

Policy Summary

PayerPremera Bluecross

PolicyPharmacotherapy of Perinatal/Infantile and Juvenile-Onset Hypophosphatasia (HPP)

Policy CodePolicy N/A

Change TypeMaterial revisions to coverage criteria and authorization length

Effective DateApr 1, 2026

Next Review DateN/A

SourceLink

On This Page

Dosing and vial strength: Dosage limitation specified; for members > 40 kg the provider must attest to permitting specialty pharmacy to determine vial strengths to minimize waste; therapy remains subject to FDA dosing/administration instructions.>40 kg

Operational dosing/vial handling requirement.

Authorization length: Initial authorization and reauthorization lengths updated — standard approvals for non-initial reviews may be issued up to 12 months.12 months

Replaces prior 6-month review interval for other reviews.

Provider must attest to permitting specialty pharmacy to determine vial strengths to minimize waste

Purpose of attestationOperational measure to reduce vial waste when dosing larger patients

Documentation Required

Documentation Requirements

Provide documentation that supports the diagnosis and ongoing need for therapy. Office visit notes should include diagnosis, genetic and laboratory test results, skeletal radiographs, and the individual's medical history documenting perinatal/infantile- or juvenile-onset HPP (onset <18 years).

Office visit notes documenting diagnosis, genetic testing results (ALPL mutation status)
Laboratory results: age-adjusted serum ALP persistently below lower limit of normal on ≥2 measurements prior to age 18; elevated plasma PLP or urinary PEA prior to age 18
Skeletal radiographs supporting HPP (e.g., rickets, bone deformities, osteomalacia, calcific periarthritis, atypical femoral fractures, recurrent metatarsal stress fractures)
Prescriber specialty: endocrinologist, geneticist, nephrologist, or rheumatologist

Denial Risk

Lack of genetically confirmed perinatal/infantile- or juvenile-onset HPP, absence of documented onset <18 years, or missing evidence of persistently low age-adjusted ALP on at least two measurements prior to age 18 may lead to denial of coverage.

Denial risk: No genetic confirmation of perinatal/infantile- or juvenile-onset HPP
Denial risk: No documentation of disease onset prior to 18 years
Denial risk: No persistently low age-adjusted ALP on ≥2 measurements prior to age 18

Measurements must be obtained prior to 18 years of age (replaces prior 'at time of diagnosis' wording)

Contextual usePersistently low ALP supports diagnosis when considered with genetic testing, elevated PLP or urinary PEA, and radiographic findings

inv-25: Relevant radiographic findings — Examples include rickets, recurrent metatarsal stress fractures, and atypical femoral fractures as specified in updated criteria

Examples of supportive radiographic findingsRickets

Recurrent metatarsal stress fracturesRecurrent metatarsal stress fractures

Atypical femoral fracturesAtypical femoral fractures (specified as an example in updated criteria)