*The RGI-C scale quantifies change over time in mineralization and bone structure.
†12 patients entered the long-term extension of the trial.3
Radiographic images
6 years of age
(at baseline)
Reproduced from Whyte MP, et al. [supplementary appendix]. JCI Insight. 2016;1(9):e85971.
11 years of age
(at 5 years)
RGI-C score: +2.67
Representations of efficacy are consistent with results seen from typical patients in the study. Individual results may vary.
6 years of age
(at baseline)
Reproduced from Whyte MP, et al. [supplementary appendix]. JCI Insight. 2016;1(9):e85971.
11 years of age
(at 5 years)
RGI-C score: +2.67
Representations of efficacy are consistent with results seen from typical patients in the study. Individual results may vary.
6 years of age
(at baseline)
Reproduced from Whyte MP, et al. [supplementary appendix]. JCI Insight. 2016;1(9):e85971.
11 years of age
(at 5 years)
RGI-C score: +2.00
Representations of efficacy are consistent with results seen from typical patients in the study. Individual results may vary.
6 years of age
(at baseline)
Reproduced from Whyte MP, et al. [supplementary appendix]. JCI Insight. 2016;1(9):e85971.
11 years of age
(at 5 years)
RGI-C score: +2.00
Representations of efficacy are consistent with results seen from typical patients in the study. Individual results may vary.
6 years of age
(at baseline)
Reproduced from Whyte MP, et al. [supplementary appendix]. JCI Insight. 2016;1(9):e85971.
11 years of age
(at 5 years)
RGI-C score: +2.67
Representations of efficacy are consistent with results seen from typical patients in the study. Individual results may vary.
aValues are statistically significant based on P<0.01.
A retrospective chart review of the natural history of hypophosphatasia in 32 untreated children with juvenile-onset hypophosphatasia and similar characteristics showed no improvement in height z scores from baseline to last assessment (61 months).6
Mean (min, max) height z score at baseline: -1.1 (-4.9, 2.6)7
Mean (min, max) height z score at last assessment: -1.1 (-4.9, 1.8)7
bValues are statistically significant based on P<0.01 vs baseline.
The normal range of height is ±2 standard deviations of the age-adjusted mean for healthy children.5
For children with hypophosphatasia, the minimal clinically important
difference (MCID) is estimated at 21 meters and
31 meters based
on 2 distribution-based methods.9
6MWT: Patients walk an indoor, flat, 30-meter walkway with cones at the beginning and end to indicate turns. At the end of 6 minutes, the total distance is recorded.10
Representations of efficacy are consistent with results seen from typical patients in the study. Individual results may vary.
cScores were normalized to percent-predicted values for age-, height-, and sex-matched healthy peers.
dValues are statistically significant based on P≤0.001 vs baseline.
STRENSIQ open-label extension: pain and disability
CHAQ discomfort index measured hypophosphatasia-related pain (eg, bone, joint, and muscle pain) and is determined by visual analog scale of pain (0=no pain, 100=very severe pain).2,4,11
*Not statistically significant.
CHAQ disability index measures activities of daily living. Scores range from 0-3, with lower scores indicating less disability.2,4,11
CHAQ is a patient/caregiver-reported assessment not validated specifically for hypophosphatasia so inferences of clinical benefit should not be made. CHAQ was developed to assess health status for children with arthritis. Interpretation of these findings is limited due to the lack of control group and potential bias introduced by use of parent-reported data for patients. Minimal clinically important difference (MCID) has not been established for the hypophosphatasia population.12,14
STRENSIQ open-label extension: strength and agility
Changes in strength and agility scores were observed up to 6 months from baseline through 7 years.
At baseline, patients showed lower strength and agility scores than healthy age-matched peers
BOT-2 measures hand and arm coordination, balance, mobility, and strength relative to healthy same-aged peers. BOT-2 is not validated specifically for hypophosphatasia so inferences of clinical benefit should not be made. It has been validated in pediatric populations (aged 4 to 21 years) with mild to moderate motor impairment.2,4,5,15,16
BOT-2 measures hand and arm coordination, balance, mobility, and strength relative to healthy same-aged peers. BOT-2 is not validated specifically for hypophosphatasia so inferences of clinical benefit should not be made. It has been validated in pediatric populations (aged 4 to 21 years) with mild to moderate motor impairment.2,4,5,15,16
References: 1. Data on file. Alexion Pharmaceuticals, Inc.
2. Whyte MP, Madson KL, Phillips D, et al. Asfotase alfa therapy
for children with hypophosphatasia. JCI Insight. 2016;1(9):e85971. 3. Whyte MP, Fujita
KP, Moseley S, Thompson DD, McAlister WH. Validation of
a novel scoring system for changes in skeletal manifestations of hypophosphatasia
in newborns, infants, and children: the radiographic global impression of change
scale. J Bone Miner Res. 2018;33(5):868-874. 4. Whyte
MP, Rockman-Greenberg C. Moseley S, Denker AE, McAlister WH. Sustained radiographic
and functional improvements with asfotase alfa treatment for up to 7 years
in children with hypophosphatasia. Oral presentation at: 8th Biennial International
Conference on Children’s Bone Health (ICCBH); June 10-13, 2017; Würzburg, Germany.
5. Whyte MP, et al. Abstract presented at: 8th Biennial International
Conference on Children’s Bone Health (ICCBH); June 10-13, 2017; Würzburg, Germany.
6. Whyte MP, Madson KL, Munns CF, et al. A retrospective,
multi-national, non-interventional, natural history study of the childhood
form of hypophosphatasia. Presented at: Endocrine Society’s 97th Annual Meeting
and Expo; March 15, 2015; San Diego, CA. 7. STRENSIQ. Package
Insert. Alexion Pharmaceuticals, Inc. 8. Data on file. Alexion
Pharmaceuticals, Inc. 9. Phillips D, Tomazos IC, Moseley S,
et al. Reliability and validity of the 6-minute walk test in hypophosphatasia.
JBMR Plus. 2019;3(6):e10131. 10. ATS Committee on Proficiency
Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines
for the six-minute walk test. Am J Respir Crit Care Med. 2002;166(1):111-117.
11. Dempster H, Porepa M, Young N, Feldman BM. The clinical
meaning of functional outcome scores in children with juvenile arthritis. Arthritis Rheum.
2001;44(8):1768-1774. 12. Klepper SE. Measures of pediatric
function. Arthritis Rheum. 2003;49(suppl 5):S5-S14. 13. Klepper SE. Measures of
pediatric function. Arthritis Care Res. 2011;63(suppl
11):S371-S382. 14. Whyte MP, Rockman-Greenberg C, Moseley
S, Denker AE, Watsky E, McAlister WH. Sustained radiographic and functional
improvements with asfotase alfa treatment for up to 7 years in children with
hypophosphatasia. Poster presented at: International Congress of Inborn Errors
of Metabolism (ICIEM); Sept 5–8, 2017; Rio de Janeiro, Brazil. 15. Bruininks RH, Bruininks BD.
Pearson. Updated October 22, 2013. Accessed April
4, 2023. http://images.pearsonclinical.com/images/Assets/BOT-2/
BOT-2_Complete_Form_Sample_Report.pdf
16. Bruininks RH, Bruininks BD. Pearson. Accessed April 4,
2023. https://
www.pearsonassessments.com/store/usassessments/en/Store/Professional-Assessments/Motor-Sensory/Bruininks-Oseretsky-Test-of-Motor-Proficiency-%7C-Second-Edition/p/100000648.html?tab=product-details
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.
Initiate STRENSIQ under the supervision of a healthcare provider with appropriate medical monitoring and support measures. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue STRENSIQ and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1)].
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.
Initiate STRENSIQ under the supervision of a healthcare provider with appropriate medical monitoring and support measures. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue STRENSIQ and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1)].
Life-threatening Hypersensitivity Reactions, Including Anaphylaxis, have been reported in STRENSIQ-treated patients. Signs and symptoms consistent with anaphylaxis included difficulty breathing, choking sensation, nausea, periorbital edema, and dizziness. These reactions have occurred within minutes after subcutaneous administration of STRENSIQ and have been observed more than 1 year after treatment initiation. Other hypersensitivity reactions have also been reported in STRENSIQ-treated patients, including vomiting, fever, headache, flushing, irritability, chills, erythema, rash, pruritus, and oral hypoesthesia. Consider the risks and benefits of re-administering STRENSIQ following a severe reaction. If the decision is made to re-administer, monitor patients for a reoccurrence of signs and symptoms of a severe hypersensitivity reaction.
Lipodystrophy: Localized lipodystrophy, including lipoatrophy and lipohypertrophy has been reported at injection sites after several months in patients treated with STRENSIQ in clinical trials. Advise patients to follow proper injection technique and to rotate injection sites.
Ectopic Calcifications: Patients with HPP are at increased risk for developing ectopic calcifications. Events of ectopic calcification, including ophthalmic (conjunctival and corneal) and renal (nephrocalcinosis, nephrolithiasis), have been reported in the clinical trial experience with STRENSIQ. There was insufficient information to determine whether or not the reported events were consistent with the disease or due to STRENSIQ. No visual changes or changes in renal function were reported resulting from the occurrence of ectopic calcifications.
Ophthalmology examinations and renal ultrasounds are recommended at baseline and periodically during treatment with STRENSIQ to monitor for signs and symptoms of ophthalmic and renal ectopic calcifications and for changes in vision or renal function.
Possible Immune-Mediated Clinical Effects: In clinical trials, most STRENSIQ-treated patients developed anti-asfotase alfa antibodies and neutralizing antibodies which resulted in reduced systemic exposure of asfotase alfa. In postmarketing reports, some STRENSIQ-treated patients with initial therapeutic response subsequently developed recurrence and worsening in disease-associated laboratory and radiographic biomarkers (some in association with neutralizing antibodies) suggesting possible immune-mediated effects on STRENSIQ’s pharmacologic action resulting in disease progression. The effect of anti-asfotase alfa antibody formation on the long-term efficacy of STRENSIQ is unknown. There are no marketed anti-asfotase alfa antibody tests. If patients experience progression of HPP symptoms or worsening of disease-associated laboratory and imaging biomarkers after a period of initial therapeutic response to STRENSIQ, consider obtaining anti-asfotase alfa antibody testing by contacting STRENSIQ Medical Information at Alexion at 1-888-765-4747 or by email at medinfo@alexion.com. Close clinical follow up is recommended.
In clinical trials, the most common adverse reactions (≥ 10%) reported were injection site reactions (63%), lipodystrophy (28%), ectopic calcifications (14%), and hypersensitivity reactions (12%). Possible immune-mediated clinical effects have been identified during post-approval use of STRENSIQ.
Laboratory tests utilizing alkaline phosphatase (ALP) as a detection reagent could result in erroneous test results for patients receiving treatment due to the presence of asfotase alfa in clinical laboratory samples. Inform laboratory personnel that the patient is being treated with STRENSIQ and discuss use of an alternative testing platform which does not utilize an ALP-conjugated test system.
Elevated serum ALP measurements detected through clinical laboratory testing are expected in patients receiving STRENSIQ due to circulating concentrations of asfotase alfa. Do not rely on serum ALP measurements for clinical decision making in patients treated with STRENSIQ.
Pregnancy & Lactation: There are no available data on STRENSIQ use in pregnant women, the presence of STRENSIQ in human milk, or the effects on the breastfed infant or on milk production, to inform a drug associated risk.
To report SUSPECTED ADVERSE REACTIONS, contact Alexion Pharmaceuticals, Inc. at 1-844-259-6783 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
STRENSIQ® (asfotase alfa) is indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).
Please see full Prescribing Information for STRENSIQ (asfotase alfa), including Boxed WARNING regarding hypersensitivity reactions including anaphylaxis.
