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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J2000-58

Original Effective Date: 03/15/16

Reviewed: 02/08/17

Revised: 03/15/17

Next Review: 02/14/18

Subject: Asfotase alfa (Strensiq®)

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by a number of loss-of-function mutations in the ALP gene, which encodes the tissue nonspecific isozyme of alkaline phosphatase (TNSALP). These mutations affect bone and mineral metabolism. Clinical presentation of an HPP patient may be highly variable by age. The disease is progressive and potentially life-threatening, leading to progressive and debilitating damage to multiple vital organs, as well as bone deformity, pain and muscle weakness, respiratory failure, seizures. Based on the age at diagnosis of skeletal disease, four types have been identified: perinatal, infantile, juvenile, and adult types of HPP. Another form of HPP has also been reported in the literature in which only dental features without skeletal findings have been described; this type is referred to “odonto-HPP.” Estimated prevalence of perinatal and infantile HPP is 1 in 100,000 newborns. Infants exhibiting symptoms within the first 6 months of life have an overall mortality of 73% at 5 years. There are currently no FDA-approved medications for HPP other than supportive treatments.

Asfotase alfa (Strensiq), a human recombinant alkaline phosphatase (ALP) fusion protein, was approved by the U.S. Food and Drug Administration (FDA) in October 2015 for the treatment of patients with perinatal/infantile- and juvenile-onset HPP.

In two prospective studies of perinatal- or infantile-onset hypophosphatasia, asfotase alfa significantly improved overall survival compared with a historical control of untreated patients at age 1 year (97% (n=68) vs 42% (n=48)), and the percentage of patients alive at point of last contact was higher with asfotase alfa use (91% vs 27%); additionally, asfotase alfa significantly improved survival without the need for a ventilator (96% (n=54) vs 31% (n=48)) at age 1 year, and the percentage of patients not on ventilation at point of last contact was also higher with asfotase alfa use (85% vs 25%). In patients requiring any form of respiratory support, 21 of 26 (81%) were alive at the last assessment (median age at assessment, 3.2 years) compared with 1 of 20 (5%) of historical controls. Combined data from 64 perinatal- or infantile-onset and 4 juvenile-onset hypophosphatasia patients showed by month 24, 74% of patients who received asfotase alfa were considered Radiographic Global Impression of Change responders (n=68, minimum increase of 2 on scale), and height and weight improved (as measured by z-score) (n=72).

Asfotase alfa increased height and weight (as measured by z-scores) in juvenile-onset hypophosphatasia patients (n=8; aged 6 to 12 years) compared with a historical cohort of untreated patients (n=32) in a 24-week prospective trial followed by an extension trial for at least 48 months. All patients who received asfotase alfa were considered Radiographic Global Impression of Change responders (minimum increase of 2 on scale) by month 54 compared with 6% of control patients after 56 months. An increase in step length by at least 1 point in either foot was also noted in 6 of 8 patients who received asfotase alfa compared with 1 of 6 control patients. The percent predicted normal values of the 6-minute walk test improved from 0% at baseline (0 of 8 patients) to 100% (6 of 6 patients) by month 48.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

Initiation of asfotase alfa (Strensiq) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with any of the following:

a. Perinatal/infantile-onset hypophosphatasia (HPP)

b. Juvenile-onset hypophosphatasia (HPP)

2. Member has skeletal abnormalities indicative of HPP – documentation from the medical record must be provided

a. Note: Examples of skeletal abnormalities include chest wall deformities, hypomineralized skeleton, rickets, nonhealing fractures.

3. Member has an alkaline phosphatase (ALP) level below age-adjusted lower limit of normal (table 1) – laboratory documentation must be provided

4. Member has a pyridoxal-5’-phosphate (PLP) level greater than two times laboratory’s upper limit of normal – laboratory documentation must be provided

5. Member has an ALPL genetic mutation – laboratory documentation must be provided

6. Member is less than 18 years of age

7. Dose does not exceed 6 mg/kg/week

Approval duration: 6 months

Continuation of asfotase alfa (Strensiq) meets the definition of medical necessity for members meeting the following criteria:

1. Authorization/reauthorization has been previously approved by Florida Blue for treatment of perinatal/infantile- or juvenile-onset HPP OR the member has previously met all indication-specific initiation criteria

2. Member has demonstrated a clinical improvement in symptoms following initiation of asfotase alfa – documentation from the medical record must be provided

3. Dose does not exceed:

a. Perinatal/infantile-onset HPP: 9 mg/kg/week

b. Juvenile-onset HPP: 6 mg/kg/week

Approval duration: 1 year

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved

• Perinatal/Infantile-Onset HPP

o Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen.

o The dose may be increased to 3 mg/kg three times per week for insufficient efficacy.

• Juvenile-Onset HPP

o Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen.

Dose Adjustments

• None

Drug Availability

• Injection: 18 mg/0.45 mL, 28 mg/0.7 mL, 40 mg/mL, or 80 mg/0.8 mL solution in single-use vials

PRECAUTIONS:

Boxed Warning

• None

Contraindications

• None

Precautions/Warnings

• Hypersensitivity Reactions

• Lipodystrophy

• Ectopic Calcifications (eye and kidneys)

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

C9399

Unclassified drugs or biologicals (Hospital Outpatient Use ONLY)

J3590

Unclassified biologics

ICD-10 Diagnoses Codes That Support Medical Necessity

E83.39

Other disorders of phosphorus metabolism

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline review date.

DEFINITIONS:

None

RELATED GUIDELINES:

None

OTHER:

Table 1. Reference Intervals for Total ALP Activity in Serum or Plasma

Age

Male/Female Reference Intervals (U/L)*

<1 month

60-320

1-11 months

70-350

1-3 years

125-320

4-6 years

150-370

7-9 years

150-440

10-11 years

150-470/150-530

12-13 years

160-500/110-525

14-15 years

130-530/55-305

16-19 years

60-270/40-120

20 years and older

40-120

* Adapted from ARUP Laboratories

REFERENCES:

  1. Alexion Pharmaceuticals. Strensiq (asfotase alfa) solution. 2015 [cited 2017-01-27]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3387574f-5eaa-4501-a71d-4cbfbd563031 /.
  2. ARUP Laboratories. Alkaline phosphatase isoenzymes, serum or plasma. ARUP Laboratories website. http://ltd.aruplab.com/tests/pub/0021020.
  3. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017-01-27]. Available from: http://www.clinicalpharmacology.com/.
  4. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2017-01-27]. Available from: http://clinicaltrials.gov/.
  5. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017-01-27]. Available from: http://www.thomsonhc.com/.
  6. Mornet E, Nunes ME. Hypophosphatasia. In: Pagon RA, Bird TD, Dolan CR, Stephen K, eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1150/. Published November 20, 2007.
  7. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017-01-27]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  8. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013;10(suppl 2):380-388.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 02/08/17.

GUIDELINE UPDATE INFORMATION:

03/15/16

New Medical Coverage Guideline.

03/15/17

Review and revision to guideline; position statement, references.

Date Printed: August 21, 2017: 07:53 PM