ModifiedPremera BluecrossPolicy N/A

Strensiq (asfotase alfa) — coverage criteria for genetically confirmed perinatal/infantile- and juvenile-onset hypophosphatasia

Policy governing medical necessity and coverage criteria for Strensiq (asfotase alfa) for treatment of genetically confirmed perinatal/infantile- and juvenile-onset hypophosphatasia; applies to pharmacy benefit management. Affects prescribing clinicians, geneticists, endocrinologists, and payers.

Policy Summary

PayerPremera Bluecross

PolicyStrensiq (asfotase alfa) coverage criteria — genetically confirmed perinatal/infantile- & juvenile-onset HPP

Policy CodePolicy N/A

Change TypeMaterial update: prescriber requirement added

Effective DateMar 24, 2025

Next Review DateN/A

Key ActionObtain prior authorization and ensure Strensiq is prescribed by or in consultation with a geneticist, endocrinologist, or specialty physician and document genetic, biochemical and radiographic evidence of HPP.

SourceLink

POLICY UPDATE CHANGES

Updated Strensiq (asfotase alfa) coverage criteria to include a prescriber requirement.

Clarified that non-formulary exception review authorizations for all drugs listed in this policy may be approved up to 12 months.

Clarified that the medications listed in this policy are subject to the product's FDA dosage and administration prescribing information.

Annual review updates with no changes to policy statements for multiple years.

perinatal/infantile & juvenileCovered HPP onset subtypes

up to 12 monthsInitial non-formulary exception approval duration

2024-07

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.

Most recent PI revision

2017-2025Policy history timeframe

Coverage Criteria for Strensiq (asfotase alfa)

Medical Necessity — Initial coverage for Strensiq (asfotase alfa)

Covered when ALL of the following are met:

Strensiq medical necessity criteria: Onset of disease is perinatal/infantile or juvenile (less than 18 years of age)

Strensiq medical necessity criteria: Genetic testing showing mutation status of the ALPL gene (encoding tissue-nonspecific alkaline phosphatase)

Strensiq medical necessity criteria: Age‑adjusted serum alkaline phosphatase (ALP) below the lower limit of normal at time of diagnosis

Strensiq medical necessity criteria: Skeletal radiographs at time of diagnosis supportive of HPP (e.g., bone deformities, osteomalacia, calcific periarthritis, or atypical fractures)

Strensiq medical necessity criteria: Strensiq (asfotase alfa) is prescribed by or in consultation with a geneticist, endocrinologist, or a physician who specializes in the condition

Duration of Approval and Reauthorization

Re-authorization/Length of approval requirements

Authorization duration and reauthorization: Initial non-formulary exception reviews may be approved up to 12 months; all other initial approvals may be approved up to 6 months.up to 12 months / up to 6 months

Authorization duration and reauthorization: Re-authorization (non-formulary exception and all other reviews) may be approved up to 12 months if drug‑specific coverage criteria are met and chart notes demonstrate continued positive clinical response supported by skeletal radiographs, ALP, plasma PLP and/or urinary PEA levels.up to 12 months

Continued clinical response must be documented in chart notes; objective measures may include radiographs and biomarkers.

Strensiq (asfotase alfa) coverage criteria

Policy includes coverage criteria for asfotase alfa; 2024 update added a prescriber requirement.

Coverage for Strensiq: Strensiq (asfotase alfa) is covered when the policy's diagnostic and clinical criteria are met; 2024 revision added a prescriber requirement that the drug be prescribed by or in consultation with a geneticist, endocrinologist, or a physician who specializes in the condition.

See Medical Necessity — Initial coverage for the full list of diagnostic and laboratory criteria (genetic confirmation, ALP, PLP or urinary PEA, and radiographic support).

All uses of Strensiq (asfotase alfa) that do not meet the policy's specified coverage criteria are considered investigational. This includes use of asfotase alfa for adult-onset hypophosphatasia (HPP) and any other indications not explicitly listed as medically necessary in this policy.

At the time the policy was originally established and in subsequent history entries, the policy has stated that all other uses of asfotase alfa beyond the covered infantile- and juvenile-onset HPP indications are investigational.

The policy history documents the original 2017 policy approval which specified that use of asfotase alfa outside of infantile- and juvenile-onset HPP was considered investigational when the policy was first adopted.

Coding and Authorization Duration

Codingmixed

No codes listed

Historical HCPCS changesHCPCS

J3490	Previously listed HCPCS code removed from policy (historical).
J3590	Previously added then removed HCPCS code (historical).

inv-09: authorization duration — up to 12 months

Authorization durationUp to 12 months for non-formulary exception approvals (initial and reauthorization as clarified); other initial approvals up to 6 months per policy

Reauthorization criteriaMay be approved up to 12 months when drug-specific criteria are met and chart notes document continued positive clinical response

Benefit managementManaged through the pharmacy benefit and subject to prior authorization processes

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Pharmacy benefit prior authorization and approval durations

Strensiq (asfotase alfa) is managed through the pharmacy benefit and requires prior authorization. Initial and renewal approvals follow the durations below; non-formulary exception requests may be approved up to 12 months when criteria are met.

Prior authorization required for Strensiq (asfotase alfa).
Non-formulary exception reviews for Strensiq may be approved for up to 12 months for initial requests.
All other reviews (non-exception routine reviews) may be approved up to 6 months for initial authorizations; reauthorizations (including non-formulary exception and other reviews) may be approved up to 12 months if drug-specific criteria are met and documentation shows continued clinical benefit (radiographs and relevant labs).

Denial Risk

Requests for all other uses of Strensiq

Requests for uses of Strensiq that are not included in the policy (including adult-onset HPP) are considered investigational and will be denied.

Clinical Background

Hypophosphatasia (HPP) is a rare inherited metabolic bone disease caused by pathogenic variants in the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). Deficiency of TNSALP leads to accumulation of substrates such as inorganic pyrophosphate and pyridoxal 5'-phosphate (PLP) that impair bone mineralization, producing a spectrum of skeletal and nonskeletal manifestations including rickets, osteomalacia, fractures, and impaired motor development. Severity varies by age of onset, with perinatal/infantile forms being the most severe. Strensiq (asfotase alfa) is an enzyme-replacement therapy approved to treat infantile- and juvenile-onset HPP.

Definitions and Key Terms

inv-19: HPP — definition and disease description (ALPL mutations, low ALP activity)

Definition (HPP)Hypophosphatasia (HPP) is a rare inherited metabolic bone disease caused by mutations in the gene encoding tissue‑nonspecific alkaline phosphatase (TNSALP), leading to low ALP activity and defective bone mineralization

Clinical featuresManifests across a spectrum by age of onset (perinatal/infantile, juvenile, adult) with rickets, osteomalacia, fractures, bone deformities, and other skeletal and nonskeletal manifestations

PathophysiologyALPL (TNSALP) mutations cause accumulation of substrates (e.g., PPi, PLP) that impair hydroxyapatite formation and bone mineralization

Severity and epidemiologyPerinatal/infantile forms are most severe and historically associated with high mortality; overall rarity noted (severe forms ~1:100,000 births)

inv-20: Genetically confirmed perinatal/infantile- or juvenile-onset HPP — onset before 18 years with genetic testing and supporting findings

Policy Summary

PayerPremera Bluecross

PolicyStrensiq (asfotase alfa) coverage criteria — genetically confirmed perinatal/infantile- & juvenile-onset HPP

Policy CodePolicy N/A

Change TypeMaterial update: prescriber requirement added

Effective DateMar 24, 2025

Next Review DateN/A

SourceLink

On This Page

Requests for Strensiq for adult-onset hypophosphatasia will be considered investigational and denied.
Non-formulary exception requests for other uses may be submitted but will be denied if requirements for investigational use are not met.

Documentation Required

Medical records must document diagnosis, testing, imaging, and clinical history

The prescriber must include documentation that the medical necessity criteria are met. The individual's medical record must contain diagnostic, genetic, laboratory, imaging, and clinical history supporting perinatal/infantile- or juvenile-onset HPP.

Office visit notes documenting the diagnosis and clinical history consistent with infantile or juvenile onset.
Genetic testing results showing ALPL mutation status.
Age-adjusted serum alkaline phosphatase (ALP) levels below the lower limit of normal at diagnosis.
Plasma pyridoxal 5'-phosphate (PLP) and/or urinary phosphoethanolamine (PEA) results supporting diagnosis.
Skeletal radiographs at time of diagnosis supporting HPP (e.g., bone deformities, osteomalacia, atypical fractures).
Record that Strensiq is prescribed by or in consultation with an appropriate specialist (geneticist, endocrinologist, or physician experienced in HPP).

Documentation Required

Documentation and approvals

Follow standard documentation and authorization processes. Approval durations and reauthorization decisions must be documented in the chart; reauthorization requires evidence of continued clinical benefit.

Document initial authorization and duration in the medical record and authorization system.
For reauthorization, submit chart notes demonstrating continued positive clinical response supported by skeletal radiographs and relevant lab values (ALP, PLP, and/or PEA).
All approvals are subject to the product's FDA dosage and administration prescribing information.

Step Therapy

Step therapy

No step therapy requirements are specified in this policy.

Providers should not expect step therapy/step edits for Strensiq under this policy.

Onset age requirementOnset of disease must be perinatal/infantile or juvenile (less than 18 years of age)

Genetic confirmationGenetic testing demonstrating mutation(s) in the ALPL gene (encoding TNSALP) is required to confirm diagnosis

Supporting diagnostic findingsAge‑adjusted serum ALP below the lower limit of normal at diagnosis AND either plasma PLP above the upper limit of normal OR urinary PEA above the upper limit of normal, plus skeletal radiographs supportive of HPP (e.g., bone deformities, osteomalacia, calcific periarthritis, atypical fractures)

Prescriber requirementStrensiq must be prescribed by or in consultation with a geneticist, endocrinologist, or physician who specializes in the condition (added in 2024 update)

inv-21: asfotase alfa — Strensiq (asfotase alfa) definition/identity

Product identityStrensiq (asfotase alfa) — a targeted enzyme replacement therapy produced by recombinant DNA technology for treatment of infantile‑ and juvenile‑onset hypophosphatasia

Indication in policyCovered for genetically confirmed perinatal/infantile‑ and juvenile‑onset HPP when policy criteria are met

Regulatory referenceSubject to the product's FDA dosage and administration prescribing information (Strensiq PI revised July 2024)