Overview

This document addresses the use of Strensiq (asfotase alfa), a tissue nonspecific alkaline phosphatase (TNSAP) recombinant isozyme developed to target underlying genetic causes of hypophosphatasia (HPP). Strensiq is indicated for the treatment of perinatal/infantile- and juvenile-onset HPP. HPP is a rare inherited error of metabolism caused by mutations of the alkaline phosphatase (ALPL) gene that results in deficient activity of alkaline phosphatase and low levels of the enzyme in serum and bone. This condition disrupts mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth.

Clinical criteria

• Generalized hypomineralization with rachitic features, chest deformities and rib fractures
• Skeletal abnormalities (e.g. short limbs, abnormally shaped chest, soft skull bone)
• Respiratory problems (e.g. pneumonia)
• Hypercalcemia
• Failure to thrive
• Severe muscular hypotonia and weakness
• Nephrocalcinosis secondary to hypercalciuria
• Swallowing problems
• Seizures

Examples of signs and symptoms in juvenile-onset HPP include:

• Failure to thrive with anorexia, nausea, and gastrointestinal problems
• Premature loss of deciduous teeth
• Short stature with bowed legs or knock knees
• Skeletal deformities (e.g. enlarged wrist and ankle joints, abnormal skull shape)
• Bone and joint pain
• Rickets
• Fractures
• Delayed walking
• Waddling gait

Prior to the development of Strensiq

Prior to the development of Strensiq, there was no specific treatment for HPP. The mortality rate for infants and children is 50-100%. FDA approval was based on four ongoing prospective, open-label studies of treatment with Strensiq using historical controls.

Ongoing studies

The ongoing studies are focused on disease development in two areas: perinatal in utero/infantile (less than 6 months of age) and childhood (greater than or equal to 6 months of age).

From the package label, a prospective open-label 24-week trial included 8 juvenile-onset HPP patients and 5 perinatal/ infantile-onset HPP patients, 6 to 12 years of age. All 8 juvenile-onset patients entered the extension study and were treated for at least 48 months. Patients who achieved a Radiolographic Global Impression of Change (RGI-C) score of 2 or higher (corresponding to substantial healing of rickets) were classified as being responders to treatment. All 8 treated patients were rated as responders by Month 54 of treatment. At last assessment, 2/32 (6%) of control patients were rated as responders. Eight of 20 (40%) control patients with juvenile-onset HPP experienced new fractures during the course of treatment. There were insufficient data to assess the effect of Strensiq on fractures. In gait/mobility by month 48, 6 of the 8 treated patients were able to walk longer distances at this time point compared to baseline gait/mobility,

Strensiq side effects

Strensiq has been reported to cause localized lipodystrophy at injection sites after several months of treatment. Patients are advised to rotate injection sites and follow proper injection technique. In clinical trials, Strensiq patients reported signs of ectopic calcification of the eye including the cornea and conjunctiva, and the kidneys. Ophthalmology examinations and renal ultrasounds are recommended at baseline and periodically during treatment.

Document history

References

Coding

Clinical Criteria

When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose.

Strensiq (asfotase alfa)

Initial requests for Strensiq (asfotase alfa) may be approved when the following criteria are met:

1. Individual has a diagnosis of one of the following:
   • A. Individual has a diagnosis of perinatal/infantile hypophosphatasia (HPP), and had onset of symptoms prior to 6 months of age; OR
   • B. Individual has a diagnosis of juvenile-onset HPP, and had onset of disease ≤ 18 years of age;
2. Documentation is provided that individual’s total serum alkaline phosphatase level is below the lower limit of normal for the individual’s age and gender at diagnosis (Whyte 2012); AND
3. Documentation is provided that individual has plasma pyridoxal 5’-phosphate levels greater than the upper limit of normal at the time of diagnosis (Whyte 2012); AND
4. One of the following:
   • A. Radiographic evidence of poor bone mineralization including flared and frayed metaphyses, severe/generalized osteopenia or widened growth plates (Whyte 2012); OR
   • B. Genetic test results that confirm infantile HPP; OR
   • C. One of the following:
     1. History or presence of nontraumatic postnatal fracture healing; OR
     2. History of elevated serum calcium; OR
     3. Functional craniosynostosis with decreased head circumference growth; OR
     4. Nephrocalcinosis; OR
     5. Rachitic chest deformity; OR
     6. Respiratory compromise; OR
     7. Vitamin B6-responsive seizures; OR
     8. Failure to thrive.

Continuation requests for Strensiq (asfotase alfa) may be approved if the following criteria are met:

2. Individual met the criteria above at the time of initiation; AND
3. There is clinically significant improvement or stabilization in clinical signs and symptoms of disease (including but not limited to respiratory status, radiographic findings, growth) following asfotase alfa therapy.

Strensiq may not be approved when the above criteria are not met and for all other indications.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

• J3490

ICD-10 Diagnosis

• E83.31
• E83.39

Unclassified drugs [when specified as Strensiq (asfotase alfa)]

Familial hypophosphatemia

Other disorders of phosphorus metabolism

Document History

Revised: 12/11/2023