7 years of demonstrated long-term safety and efficacy data1-8
| Infants / young children | Adults/adolescents | |||
|---|---|---|---|---|
|
|
Study 11,2,8 ENB-002-08/ENB-003-08 |
Study 21,6 ENB-010-10 |
Study 31,3,10 ENB-006-09/ENB-008-10 |
Study 47
ENB-009-10 |
|
Age at inclusion
|
≤3 years | ≤5 years | 6-12 years | 13-65 years |
|
Description
|
Prospective, single-arm trial and extension in patients with severe perinatal/infantile-onset HPP | Prospective, open-label, multicenter, single-arm trial in patients with perinatal/infantile-onset HPP | Prospective, open-label trial and extension in patients with juvenile- or perinatal/infantile-onset HPP | Multicenter, randomized, open-label concurrent control trial, including adolescents and adults with pediatric-onset HPP |
| Duration | 7 years | 6 years | 7 years | 5 years |
|
Primary treatment phase
|
6 months | 1-6 years | 6 months | 6 months |
|
Extension
|
6.5 years | 1-6 years | 6.5 years | 4.5 years |
|
N
|
11 | 69 | 13(9 reached adolescence during the studya) | 19 (13 adults,b 6 adolescentsa) |
STRENSIQ has been rigorously studied across 8 clinical trials, with over 1,500 patient-years of registry data, and more than 7 years of postmarket experience.12-14
Clinical practice guidelines for hypophosphatasia are not currently available in the United States. When considering treatment, healthcare providers should use their clinical judgment based on individual patient needs.15,16
aThese data reflect exposure to STRENSIQ in 99 patients with perinatal/infantile- or juvenile-onset HPP (age 1 day to 58 years) treated with STRENSIQ, most for more than 2 years (range 1 day to 312 weeks [78 months]): 51 patients received at least 96 weeks (24 months) of treatment and 39 patients received 168 weeks (42 months) or more of treatment.
bAdverse reactions are from the combined period of 6 mg/kg and above (ie, total drug exposure regardless of starting dose and intermediary doses as long as the patient reached doses >6 mg/kg).
cOther injection site reactions include injection site rash, inflammation, papule, hemorrhage, hematoma, urticaria, warmth, calcification, mass, scar, and cellulitis.
dOther lipodystrophy includes lipohypertrophy.
eOther hypersensitivity reactions include erythema/redness, pyrexia/fever, irritability, nausea, pain, rigor/chills, oral hypoesthesia, headache, flushing, and anaphylaxis.
| Perinatal/Infantile-onset HPP | Juvenile-onset HPP | |||
|---|---|---|---|---|
|
Adverse Reaction Category or Term |
STRENSIQ ≤6 mg/kg per week (N=66) n (%) |
STRENSIQ >6 mg/kg per weekb (N=13) na (%) |
TOTAL (N=79) n (%) |
STRENSIQ (N=20) n (%) |
|
Injection site reactions
|
38 (58) | 6 (46) | 44 (56) | 18 (90) |
| Erythema | 29 (44) | 3 (23) | 32 (41) | 15 (75) |
| Discoloration/ hypopigmentation | 11 (17) | 1 (8) | 12 (15) | 8 (40) |
| Pain/tenderness | 10 (15) | 1 (8) | 11 (14) | 8 (40) |
| Pruritus/Itching | 10 (15) | 0 (0) | 10 (13) | 7 (35) |
| Swelling | 8 (12) | 0 (0) | 8 (10) | 6 (30) |
| Induration | 9 (14) | 1 (8) | 10 (13) | 3 (15) |
| Macule | 4 (6) | 0 (0) | 4 (5) | 7 (35) |
| Reaction, not otherwise specified | 6 (9) | 1 (8) | 7 (9) | 4 (20) |
| Bruising | 6 (9) | 0 (0) | 6 (8) | 4 (20) |
| Nodule | 2 (3) | 0 (0) | 2 (3) | 2 (10) |
| Other injection site reactionsc | 10 (15) | 3 (23) | 13 (17) | 4 (20) |
|
Ectopic calcifications
|
3 (5) | 0 (0) | 13 (17) | 4 (20) |
|
Lipodystrophy
|
12 (18) | 0 (0) | 3 (4) | 11 (55) |
| Injection site atrophy | 4 (6) | 2 (15) | 6 (8) | 8 (40) |
| Injection site hypertrophy | 5 (8) | 0 (0) | 5 (6) | 6 (30) |
| Other lipodystrophyd | 4 (6) | 0 (0) | 4 (5) | 1 (5) |
|
Hypersensitivity reactions
|
7 (11) | 3 (23) | 10 (13) | 2 (10) |
| Vomiting/emesis | 2 (3) | 2 (15) | 4 (5) | 2 (10) |
| Other hypersensitivity reactionse | 6 (9) | 2 (15) | 8 (10) | 2 (10) |
aThese data reflect exposure to STRENSIQ in 99 patients with perinatal/infantile- or juvenile-onset HPP (age 1 day to 58 years) treated with STRENSIQ, most for more than 2 years (range 1 day to 312 weeks [78 months]): 51 patients received at least 96 weeks (24 months) of treatment and 39 patients received 168 weeks (42 months) or more of treatment.
bAdverse reactions are from the combined period of 6 mg/kg and above (ie, total drug exposure regardless of starting dose and intermediary doses as long as the patient reached doses >6 mg/kg).
cOther injection site reactions include injection site rash, inflammation, papule, hemorrhage, hematoma, urticaria, warmth, calcification, mass, scar, and cellulitis.
dOther lipodystrophy includes lipohypertrophy.
eOther hypersensitivity reactions include erythema/redness, pyrexia/fever, irritability, nausea, pain, rigor/chills, oral hypoesthesia, headache, flushing, and anaphylaxis.
Clinical practice guidelines for hypophosphatasia are not currently available in the United States. When considering treatment, healthcare providers should use their clinical judgment based on individual patient needs.15,16
References: 1. STRENSIQ. Package Insert. Alexion Pharmaceuticals, Inc. 2. Whyte MP, Greenberg CR, Salman NJ, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012;366(10):904-913. 3. Whyte MP, Madson KL, Phillips D, et al. Asfotase alfa therapy for children with hypophosphatasia. JCI Insight. 2016;1(9):e85971. 4. Whyte MP, Rockman-Greenberg C, Moseley S, Denker AE, McAlister W. Sustained radiographic and functional improvements with asfotase alfa treatment from up to 7 years in children with hypophosphatasia. Presented at: 8th Biennial International Conference on Children's Bone Health (ICCBH); June 10-13, 2017; Wurzburg, Germany. 5. Whyte M, Bishop N, Hasan J, et al. Safety profile of asfotase alfa treatment of patients with hypophosphatasia: a pooled analysis. J Endocr Soc. 2019;3(suppl 1):OR13-4. 6. Hofmann CE, Harmatz P, Vockley J, et al. Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study. J Clin Endocrinol Metab. 2019;104(7):2735-2747. 7. Kishnani PS, Rockman-Greenberg C, Rauch F, et al. Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. Bone. 2019;121:149-162. 8. Whyte MP, Simmons JH, Moseley S, et al. Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial. Lancet Diabetes Endocrinol. 2019;7(2):93-105. 9. Data on file. Alexion Pharmaceuticals, Inc. 10. 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. 11. Whyte MP, Bishop N, Hasan J, et al. Safety profile of asfotase alfa treatment of patients with hypophosphatasia: a pooled analysis. Poster presented at: 9th Biennial International Conference on Children’s Bone Health (ICCBH); June 22-25, 2019; Salzburg, Austria. 12. NIH US National Library of Medicine. ClinicalTrials.gov. Accessed April 20, 2023. https://clinicaltrials.gov/ct2/results?cond=hypophosphatasia&term=asfotase+alfa&cntry=&state=&city=&dist= 13. FDA approves Strensiq™ (asfotase alfa) for treatment of patients with perinatal-, infantile- and juvenile-onset hypophosphatasia (HPP). News release. Alexion Pharmaceuticals, Inc. October 23, 2015. Accessed April 3, 2023. https://media.alexion.com/news-releases/news-release-details/fda-approves-strensiqtm-asfotase-alfa-treatment-patients 14. Data on file. Alexion Pharmaceuticals, Inc. 15. Rockman-Greenberg C, Josse R, Francis M, Mhanni A. Impact of discontinuing 5 years of enzyme replacement treatment in a cohort of 6 adults with hypophosphatasia: A case series. Bone Rep. 2022;17:101617. 16. Bianchi ML, Bishop NJ, Guañabens N, et al; Rare Bone Disease Action Group of the European Calcified Tissue Society. Hypophosphatasia in adolescents and adults: overview of diagnosis and treatment. Osteoporos Int. 2020;31(8):1445–1460.
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.
