Coverage Policy Manual
Policy #: 2017004
Category: Pharmacy
Initiated: January 2017
Last Review: January 2024
  Asfotase alfa (e.g. Strensiq®)
Description:
Asfotase alfa is an enzyme replacement therapy for treatment of perinatal/infantile- and juvenile-onset hypophosphatasia (HPP) (FDA, 2015).   HPP is caused by loss-of- function mutations in the tissue nonspecific alkaline phosphatase (TNSALP) enzyme, which is encoded by the alkaline phosphatase (ALP) gene. TNSALP is responsible for formation of an essential mineral in normal bone; deficient TNSALP results in defective bone mineralization that can result in bone and skeletal system abnormalities, as well as systemic complications such as muscle weakness and respiratory failure. Asfotase alfa replaces the deficient TNSALP in individuals with HPP (Bishop, 2016).  Asfotase alfa was approved by the FDA in October 2015 (FDA, 2015).   It is given by subcutaneous injection.
 
Regulatory Status
 
Asfotase alfa (e.g., Strensiq®) received FDA approval in October 2015 for the treatment of individuals with perinatal/infantile- and juvenile- onset hypophosphatasia (FDA, 2015).
 
Coding
 
See CPT/HCPCS Code section below.
 
Policy/
Coverage:
Effective April 01, 2018, Prior Approval is required for asfotase alfa (e.g., Strensiq®).
 
Asfotase alfa is not covered under the medical benefit. Please check the member’s pharmacy benefit for coverage. This policy applies to members whose plan utilizes AR BCBS pharmacy and has asfotase alfa as a formulary option. (Please see Coverage Policy 2020005, Self-Administered Medication)
 
Effective January 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Note: The use of asfotase alfa (e.g., Strensiq®) in individuals greater than 17 years of age for the treatment of any indication is not covered. (Choida, 2019) See statement of non-coverage below.
 
INITIAL TREATMENT (6 month approval for juvenile-onset, 12 month approval for perinatal/infantile-onset):
 
Asfotase alfa meets member benefit certificate primary coverage criteria that there be scientific evidence of effectivenss in improving health outcomes for the treatment of individuals with perinatal/infantile/ juvenile- onset hypophosphatasia (HPP) (FDA, Strensiq, 2015) when ALL the below criteria are met:
 
1. The onset of the disease as perinatal/infantile or juvenile; AND  
2. Total serum alkaline phosphatase is below the lower limit of normal for the individual's age and gender at diagnosis (Whyte, 2012); AND  
3. Plasma pyridoxal 5'-phosphate levels are greater than the upper limit of normal at the time of diagnosis (Whyte, 2012); AND
4. The diagnosis was confirmed by (Childa, 2019):
a. The presence of mutation(s) in the ALPL gene as detected by ALPL molecular genetic testing; OR
b. The diagnosis is supported by the following radiographic skeletal abnormalities:  poor bone mineralization such as flared and frayed metaphyses, severe/generalized osteopenia or widened growth plates; OR
c. One or more of the following:
i. History or presence of nontraumatic postnatal fracture healing; OR
ii. History of elevated serum calcium; OR
iii. Functional craniosynostosis with decreased head circumference growth; OR  
iv. Nephrocalcinosis; OR
v. Rachitic chest deformity; OR
vi. Respiratory compromise; OR
vii. Vitamin B6-responsive seizures; OR
viii. Failure to thrive; OR
ix. Hypotonia; AND
5. Will not be used in the following circumstances:
a. Individual is > 17 years of (Choida, 2019); OR
b. 80 mg vials of asfotase alfa in children weighing < 40 kg; AND
6. Must be dosed in accordance with the FDA label.
 
CONTINUED TREATMENT (12-month approval or until individual reaches 17 years of age, whichever is less) (Chida, 2019)
 
1. Continued treatment will require that coverage criteria are met at the time of initiation; AND
2. The individual has demonstrated clinical improvement in symptoms/signs with asfotase alfa therapy.
 
Dosage and Administration
Dosing per FDA Guidelines
 
Perinatal/Infantile-Onset HPP
    • Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week.
    • The dose may be increased to 3 mg/kg three times per week for insufficient efficacy.
 
Juvenile-Onset HPP
    • Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week or 1 mg/kg administered six times per week.
 
Asfotase alfa is available as 18 mg/0.45 mL, 28 mg/0.7 mL, 40 mg/mL, or 80 mg/0.8 mL solution in single-dose vials.
 
Please see FDA label guidelines for additional guidelines.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Asfotase alfa, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of Asfotase alfa, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective January 15, 2022 to December 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Note: The use of asfotase alfa (e.g., Strensiq®) in patients greater than 17 years of age for the treatment of any indication is not covered. (Choida, 2019) See statement of non-coverage below.
 
INITIAL TREATMENT (6 month approval for juvenile-onset, 12 month approval for perinatal/infantile-onset)
Asfotase alfa meets member benefit certificate primary coverage criteria for the treatment of patients with perinatal/infantile/ juvenile- onset hypophosphatasia (HPP) (FDA, Strensiq, 2015) when ALL of the below criteria are met:
 
1. The onset of the disease as perinatal/infantile or juvenile, AND  
2. Total serum alkaline phosphatase is below the lower limit of normal for the individual's age and gender at diagnosis (Whyte, 2012); AND  
3. Plasma pyridoxal 5'-phosphate levels are greater than the upper limit of normal at the time of diagnosis (Whyte, 2012), AND
4. The diagnosis was confirmed by (Childa, 2019):
a. the presence of mutation(s) in the ALPL gene as detected by ALPL molecular genetic testing, OR
b. The diagnosis is supported by the following radiographic skeletal abnormalities:  poor bone mineralization such as flared and frayed metaphyses, severe/generalized osteopenia or widened growth plates, OR
c. One or more of the following:
      • History or presence of nontraumatic postnatal fracture healing;  
      • History of elevated serum calcium;  
      • Functional craniosynostosis with decreased head circumference growth; OR  
      • Nephrocalcinosis;  
      • Rachitic chest deformity;  
      • Respiratory compromise;  
      • Vitamin B6-responsive seizures;  
      • Failure to thrive
      • Hypotonia
 
Dosage and Administration
 
Perinatal/Infantile-Onset HPP
    • Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week.
    • The dose may be increased to 3 mg/kg three times per week for insufficient efficacy.
Juvenile-Onset HPP
    • Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week or 1 mg/kg administered six times per week.
 
Please see FDA label guidelines for additional guidelines.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
CONTINUED TREATMENT (12 month approval or until patient reaches 17 years of age, whichever is less) (Childa, 2019)
 
  1. Continued treatment will require that coverage criteria are met at the time of initiation; AND
  2. The individual has demonstrated clinical improvement in symptoms/signs with asfotase alfa therapy.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Asfotase alfa (Strensiq®) for the treatment of any other indications or any other circumstances than those outlined above does not meet member benefit certificate primary coverage criteria.
 
For members with contracts without primary coverage criteria, the use of Asfotase alfa (Strensiq®) for the treatment of any other indications or any other circumstances than those outlined above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of asfotase alfa (Strensiq®) in patients greater than 17 years of age for the treatment of any indication does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.(Choida, 2019)
 
For members with contracts without primary coverage criteria, the use of asfotase alfa (Strensiq®) for the treatment of patients greater than 17 years of age for any indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of 80 mg vials of asfotase alfa in children weighing less than 40 kg does not meet member benefit certificate primary coverage criteria.
 
For members without primary coverage criteria, the use of 80 mg vials of asfotase alfa in children weighing less than 40 kg is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective January 17, 2019 to January 14, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
INITIAL TREATMENT (6 month approval for juvenile-onset, 12 month approval for perinatal/infantile-onset)
 
Asfotase alfa meets member benefit certificate primary coverage criteria for the treatment of patients with perinatal/infantile/ juvenile- onset hypophosphatasia (HPP) (FDA, Strensiq, 2015) when ALL of the below criteria are met:
1. The onset of the disease as perinatal/infantile or juvenile, AND  
2. Total serum alkaline phosphatase is below the lower limit of normal for the individual's age and gender at diagnosis (Whyte, 2012); AND  
3. Plasma pyridoxal 5'-phosphate levels are greater than the upper limit of normal at the time of diagnosis (Whyte, 2012), AND
4. The diagnosis was confirmed by (Childa, 2019):
a. the presence of mutation(s) in the ALPL gene as detected by ALPL molecular genetic testing, OR
b. The diagnosis is supported by the following radiographic skeletal abnormalities:  poor bone  mineralization such as flared and frayed metaphyses, severe/generalized osteopenia or widened growth plates, OR
c. One or more of the following:
          • History or presence of nontraumatic postnatal fracture healing;  
          • History of elevated serum calcium;  
          • Functional craniosynostosis with decreased head circumference growth; OR  
          • Nephrocalcinosis;  
          • Rachitic chest deformity;  
          • Respiratory compromise;  
          • Vitamin B6-responsive seizures;  
          • Failure to thrive
          • Hypotonia
 
Dosage and Administration
 
Per FDA label guidelines.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
 
CONTINUED TREATMENT (12 month approval or until patient reaches 17 years of age, whichever is less) (Childa, 2019)
 
    1. Continued treatment will require that coverage criteria are met at the time of initiation; AND
    2. The individual has demonstrated clinical improvement in symptoms/signs with asfotase alfa therapy.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Asfosase alfa (Strensiq®) for the treatment of any other indications or any other circumstances than those outlined above does not meet member benefit certificate primary coverage criteria.
 
For members with contracts without primary coverage criteria, the use of Asfosase alfa (Strensiq®) for the treatment of any other indications or any other circumstances than those outlined above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of asfotase alfa (Strensiq®) in patients greater than 17 years of age for the treatment of any indication does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.(Choida, 2019)
 
For members with contracts without primary coverage criteria, the use of asfotase alfa (Strensiq®) for the treatment of patients greater than 17 years of age for any indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of 80 mg vials of asfotase alfa in children weighing less than 40 kg does not meet member benefit certificate primary coverage criteria.
 
For members without primary coverage criteria, the use of 80 mg vials of asfotase alfa in children weighing less than 40 kg is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective February 2018 - January 16, 2019
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
INITIAL TREATMENT (6 month approval for juvenile-onset, 12 month approval for perinatal/infantile-onset)
 
Asfotase alfa meets primary coverage criteria for the treatment of patients with perinatal/infantile/ juvenile- onset hypophosphatasia (HPP) when ALL of the below criteria are met:
1. The onset of the disease as perinatal/infantile or juvenile, and  
2. Total serum alkaline phosphatase is below the lower limit of normal for the individual's age and gender at diagnosis; and  
3. Plasma pyridoxal 5'-phosphate levels are greater than the upper limit of normal at the time of diagnosis, and  
4. The diagnosis was confirmed by:
a. the presence of mutation(s) in the ALPL gene as detected by  ALPL molecular genetic testing, OR
b. The diagnosis is supported by the following radiographic skeletal abnormalities:  poor bone mineralization such as flared and frayed metaphyses, severe/generalized osteopenia or widened growth plates, OR
c. One or more of the following:
          • History or presence of nontraumatic postnatal fracture healing;  
          • History of elevated serum calcium;  
          • Functional craniosynostosis with decreased head circumference growth; or  
          • Nephrocalcinosis;  
          • Rachitic chest deformity;  
          • Respiratory compromise;  
          • Vitamin B6-responsive seizures;  
          • Failure to thrive
          • Hypotonia
5. The prescribed regimen is in compliance with FDA-approved dosing:
    • For perinatal/infantile onset HPP, the dose is less than 3mg/kg three times per week OR 1mg/kg  six times per week.
    • For juvenile-onset HPP, the dose is less than 2mg/kg three times per week or 1mg/kg six times per week.
 
CONTINUED TREATMENT (12 month approval or until patient reaches 17 years of age, whichever is less)
 
  1. Continued treatment will require that coverage criteria are met at the time of initiation; and  
  2. The individual has demonstrated clinical improvement in symptoms/signs with asfotase alfa therapy.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Asfosase alfa (Strensiq®) for the treatment of any other indications or any other circumstances than those outlined above does not meet member benefit certificate primary coverage criteria.
 
For members with contracts without primary coverage criteria, the use of Asfosase alfa (Strensiq®)  for the treatment of any other indications or any other circumstances than those outlined above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of asfotase alfa (Strensiq®) in patients  greater than 17 years of age for the treatment of any indication does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of asfotase alfa (Strensiq®) for the treatment of patients greater than 17 years of age for any indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of 80 mg vials of asfotase alfa in children weighing less than 40 kg does not meet member benefit certificate primary coverage criteria.
 
For members without primary coverage criteria, the use of 80 mg vials of asfotase alfa in children weighing less than 40 kg is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
 
Effective Prior To February 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
INITIAL TREATMENT
 
Asfotase alfa meets primary coverage criteria for the treatment of patients with perinatal/infantile/ juvenile- onset hypophosphatasia (HPP) when ALL of the below criteria are met:
 
    1. The onset of the disease as perinatal/infantile or juvenile, and  
    2. Total serum alkaline phosphatase is below the lower limit of normal for the individual's age and gender at diagnosis; and  
    3. Plasma pyridoxal 5'-phosphate levels are greater than the upper limit of normal at the time of diagnosis, and  
    4. The diagnosis was confirmed by:
            1. the presence of mutation(s) in the ALPL gene as detected by  ALPL molecular genetic testing, OR
            2. The diagnosis is supported by the following radiographic skeletal abnormalities:  poor bone mineralization such as flared and frayed metaphyses, severe/generalized osteopenia or widened growth plates, OR
            3. One or more of the following:
                    • History or presence of nontraumatic postnatal fracture healing;  
                    • History of elevated serum calcium;  
                    • Functional craniosynostosis with decreased head circumference growth; or  
                    • Nephrocalcinosis;  
                    • Rachitic chest deformity;  
                    • Respiratory compromise;  
                    • Vitamin B6-responsive seizures;  
                    • Failure to thrive
                    • Hypotonia
5. The prescribed regimen is in compliance with FDA-approved dosing:
            1. For perinatal/infantile onset HPP, the dose is less than 3mg/kg three times per week OR 1mg/kg  six times per week.
            2. For juvenile-onset HPP, the dose is less than 2mg/kg three times per week or 1mg/kg six times per week.
            3. 80 mg vials will not be allowed for children weighing less than 40 kg.  
 
CONTINUED TREATMENT
 
        1. Continued treatment will require that coverage criteria are met at the time of initiation; and  
        2. The individual has demonstrated clinical improvement in symptoms/signs with asfotase alfa therapy.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of asfotase alfa (Strensiq®) for the treatment of any other indications or any other circumstances than those outlined above does not meet member benefit certificate primary coverage criteria.
 
For members with contracts without primary coverage criteria, the use of asfotase alfa (Strensiq®)  for the treatment of any other indications or any other circumstances than those outlined above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of asfotase alfa (Strensiq®) in patients  greater than 17 years of age for the treatment of any indication does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of asfotase alfa (Strensiq®) for the treatment of patients greater than 17 years of age for any indication is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of 80 mg vials of asfotase alfa in children weighing less than 40 kg does not meet member benefit certificate primary coverage criteria.
 
For members without primary coverage criteria, the use of 80 mg vials of asfotase alfa in children weighing less than 40 kg is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
 
Rationale:
Asfotase alfa was evaluated in a 24-week prospective study of 11 patients  (age of 3 years or less) with severe HPP, with symptoms occurring before 6 months of age.  Severe HPP was defined as biochemical, medical history, and radiographic evidence of HPP as well as the presence of one of the following: chest deformity, vitamin B6-dependent seizures or failure to thrive.  One patient dropped out due to adverse effects.  The primary endpoints were met, with  Radiographic Global Impression of Change score (RGI-C) scores improved in 9 out of 10 patients and a statistically significant improvement in RSS scores.  Secondary end points showed decrease in need for mechanical ventilation and improvements in motor development (Whyte, 2012).
 
The tolerability, safety, and efficacy in HPP was evaluated in an open-label prospective study compared to historical controls. A total of 48 patients were enrolled between 2 different studies. Enrolled patients had symptom onset prior to 6 months of age. Enrollment criteria required one of the following:  1) TNSALP gene mutation, 2) serum ALP below normal limits and either pyridoxal 5′-phosphate or urinary phosphoethanolamine above upper limit of normal, or 3) serum ALP below normal limits and radio graphic findings consistent with HPP.  In addition, patients had to have one of the following: 1) respiratory compromise, 2)rachitic chest deformity, or 3)vitamin b-6 dependent seizures. Mortality was significant reduced (p<.0001)  for the asfotase Alfa group, with survival at 1 year of age of 95% of treated patients vs 42% for history controls.  Survival at 5 years was also improved, with 84% survival for treated  patients vs 27% of historical controls (Whyte, 2016).
 
Asfotase alfa efficacy beyond one year was established by a study comparing 13 children between the ages of 6 and 12 with infantile HPP or childhood HPP treated with asfotase alfa to historical controls. There were variations between the group, including average age and median serum ALP level (being lower in the historical control group). The primary endpoint was skeletal radiographic changes, as evaluated by the median Radiographic Global Impression of Change score (RGI-C).  75% of treated patients were considered “responders” with an RGI-C ≥2 at 2 years, whereas no controls had improvements in RGI-C (Whyte, 2016).
 
In a multinational, randomized, open label study (NCT01163149; EudraCT 2010-019850-42), safety and efficacy were evaluated in adults and adolescents 13-66 years of age with HPP.  The study comprised one  a 6-month primary treatment period and a 4.5 year extension phase. 19 patients were randomized to receive asfotase alfa 0.3 mg/kg/day subcutaneously, asfotase alfa 0.5 mg/kg/day, or no treatment for 6 months. In the extension phase, patients received asfotase alfa (0.5mg/kg/day for 6 month -1 year, then 1 mg/kg/day 6 days/week). During the primary treatment period, changes from baseline to month 6 in plasma pyridoxal 5’-phosphate (PLP) and inorganic pyrophosphate (PPi) concentrations (coprimary efficacy measure) were greater in the combined asfotase alfa group compared with the control group reaching statistical significance for PLP (P = 0.0285) but not for PPi (P = 0.0715). The changes in both PLP and PPi after 6 months and over 5 yrs of treatment with asfotase alfa were significant (P<0.05).  Secondary efficacy measures included transiliac crest histomorphometry, dual-energy X-ray absorptiometry (DXA), and the 6-Minute Walk Test (6MWT). A significant decrease from Baseline in mineralization lag time was observed in the combined asfotase alfa group at Year 1. There were no significant differences between treated and control patients in DXA mean bone mineral density results at 6 months; Z-scores and T-scores were within the expected range for age at Baseline and remained so over 5 years of treatment. On the 6MWT, median (min, max) distance walked increased from 355 (10, 620; n = 19) meters before treatment to 450 (280, 707; n = 13) meters at 5 years (P < 0.05). Results for the exploratory outcome measures suggested improvements in gross motor function, muscle strength, and patient-reported functional disability over 5 years of treatment. There were no deaths during this study. Asfotase alfa was generally well tolerated; the most common adverse events were mild to moderate injection site reactions. This study suggests that in adults and adolescents with pediatric-onset HPP, treatment with asfotase alfa is associated with normalization of circulating TNSALP substrate levels and improved functional abilities. (Kishnani et al. 2018)
 
2019 Update
A literature search conducted through December 2018 did not reveal any new information that would prompt a change in the coverage statement.
 
2020 Update
A literature search conducted through January 2020 did not reveal any new information that would prompt a change in the coverage statement.
 
February 2020 Update
A multinational, randomized, open-label study (NCT01163149; EudraCT 2010-019850-42) was conducted to evaluate the efficacy and safety of asfotase alfa in adults and adolescents 13–66 years of age with hypophosphatasia (HPP). The study comprised a 6-month primary treatment period and a 4.5-year extension phase. In the primary treatment period, 19 patients were randomized to receive asfotase alfa 0.3 mg/kg/d subcutaneously (SC; n=7), asfotase alfa 0.5 mg/kg/d SC (n=6), or no treatment (control; n=6) for 6 months. In the extension phase, patients received asfotase alfa (0.5 mg/kg/d for 6 month–1 year, then 1 mg/kg/d 6 d/wk). During the primary treatment period, changes from Baseline to Month 6 in plasma PLP and PPi concentrations (coprimary efficacy measure) were greater in the combined asfotase alfa group compared with the control group, reaching statistical significance for PLP (P=0.0285) but not for PPi (P=0.0715). However, for the total cohort, the within subject changes in both PLP and PPi after 6 months and over 5 years of treatment with asfotase alfa were significant (P < 0.05). Secondary efficacy measures included transiliac crest histomorphometry, dual-energy X-ray absorptiometry (DXA), and the 6-Minute Walk Test (6MWT). A significant decrease from Baseline in mineralization lag time was observed in the combined asfotase alfa group at Year 1. There were no significant differences between treated and control patients in DXA mean bone mineral density results at 6 months; Z-scores and T-scores were within the expected range for age at Baseline and remained so over 5 years of treatment. On the 6MWT, median (min, max) distance walked increased from 355 (10, 620; n=19) meters before treatment to 450 (280, 707; n=13) meters at 5 years (P < 0.05). Results for the exploratory outcome measures suggested improvements in gross motor function, muscle strength, and patient reported functional disability over 5 years of treatment. There were no deaths during this study. Asfotase alfa was generally well tolerated; the most common adverse events were mild to moderate injection site reactions. This study suggests that in adults and adolescents with pediatric-onset HPP, treatment with asfotase alfa is associated with normalization of circulating TNSALP substrate levels and improved functional abilities. Although statistical significance on the prespecified coprimary efficacy measure (reductions in PLP and PPi at Month 6) was not met, the totality of the data indicates efficacy of asfotase alfa in the treatment of this older population of patients with HPP. (Kishani, Rockman-Greenberg, Rauch, et al., 2019)
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2021. No new literature was identified that would prompt a change in the coverage statement.
 
2022 Update
A 13-week, Phase 2a, open-label study enrolled adults (aged ≥18 years) with pediatric-onset HPP. They were randomized 1:1:1 to receive a single subcutaneous dose of asfotase alfa (0.5, 2.0, or 3.0 mg/kg) at Week 1, then 3 times per week (i.e., 1.5, 6.0, or 9.0 mg/kg/wk) starting at Week 3 for 7 weeks. Key outcome measures included change from Baseline to before the third dose during Week 9 (trough) in plasma PPi (primary outcome measure) and PLP (secondary outcome measure).
 
Twenty-seven adults received asfotase alfa 0.5 (n = 8), 2.0 (n = 10), and 3.0 (n = 9) mg/kg; all completed the study. Median (range) age was 45 (18-77) years; most patients were white (96%) and female (59%). Median plasma PPi and PLP concentrations decreased from Baseline to Week 9 in all 3 cohorts. Differences in least squares mean (LSM) changes in PPi were significant with 2.0 mg/kg (p = 0.0008) and 3.0 mg/kg (p < 0.0001) vs. 0.5 mg/kg. Differences in LSM changes in PLP were also significant for 2.0 mg/kg (p = 0.0239) and 3.0 mg/kg (p = 0.0128) vs. 0.5 mg/kg. Injection site reactions were the most frequent treatment-emergent adverse event (78%), showing increasing frequency with increasing dose.
 
Adults with pediatric-onset HPP receiving asfotase alfa at 6.0 mg/kg/wk (the recommended dose) or 9.0 mg/kg/wk had greater reductions in circulating PPi and PLP concentrations compared with a lower dose of 1.5 mg/kg/wk. (Seefried L, Kishnani PS, Moseley S, et.al., 2021)
 
2023 Update  
A literature search conducted through November 2022 did not reveal any new information that would prompt a change in the coverage statement.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2024. No new literature was identified that would prompt a change in the coverage statement.
CPT/HCPCS:
J3490Unclassified drugs
References: Childa V and Bubbear JH(2019) Update on the management of hypophosphatasia, Ther Adv Musculoskelet Dis. 2019; 11: 1759720X19863997.

Kishnani P, Rockman-Greenberg C, Rauch F, et al. (2018),(2018) Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. Bone 2019 Apr;121:149-162. doi: 10.1016/j.bone.2018.12.011. Epub 2018 Dec 18.

Kishnani PS, Rockman-Greenberg C, Rauch F, et al.(2019) Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. Bone. 2019;121:149–162. doi:10.1016/j.bone.2018.12.011

Seefried L, Kishnani PS, Moseley S, Denker AE, Watsky E, Whyte MP, Dahir KM.(2021) Pharmacodynamics of asfotase alfa in adults with pediatric-onset hypophosphatasia. Bone. 2021 Jan;142:115664. doi: 10.1016/j.bone.2020.115664. Epub 2020 Sep 26. PMID: 32987199.

Strensiq® [package insert]. Cheshire, CT: Alexion Pharmaceuticals Inc; 2015.

Whyte MP, Greenberg CR, Salman NJ, et al.(2012) Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012; 366(10):904-913.

Whyte MP, Madson KL, Phillips D, et al.(2016) Asfotase alfa therapy for children with hypophosphatasia. JCI Insight. 2016;1(9):e85971. doi:10.1172/jci.insight.85971.

Whyte MP, Rockman-Greenberg C, Ozono K, et al.(2016) Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. 2016;101(1):334-342. doi:10.1210/jc.2015-3462.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association.