Asfotase Alfa (Monograph)

Brand name: Strensiq
Drug class: Enzymes

Medically reviewed by Drugs.com on Jun 10, 2025. Written by ASHP.

Warning

Anaphylaxis reported to occur during early course of enzyme replacement therapy and after extended duration of therapy.
Initiate asfotase alfa therapy under supervision of a clinician with appropriate medical monitoring and support measures.
If severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue therapy and immediately initiate appropriate medical treatment, including epinephrine administration.

Introduction

Biosynthetic (recombinant DNA origin) form of human tissue-nonspecific alkaline phosphatase (TNSALP).

Uses for Asfotase Alfa

Hypophosphatasia

Enzyme replacement therapy in patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP); designated an orphan drug by FDA for use in these conditions.

Improves overall and invasive ventilation-free survival in patients with perinatal/infantile-onset HPP; improvements in growth, radiologic scores, histologic parameters, and biochemical markers also observed in such patients.

Improves growth, mobility, radiologic scores, histologic parameters, and biochemical markers in patients with juvenile-onset HPP.

HPP registry established to monitor variability and progression of HPP and long-term effects of asfotase alfa. Encourage patients and their caregivers to participate in this voluntary program. For more information, visit [Web].

Asfotase Alfa Dosage and Administration

General

Patient Monitoring

Perform ophthalmology examinations and renal ultrasounds at baseline and periodically during treatment.

Dispensing and Administration Precautions

Initiate asfotase alfa therapy under the supervision of a clinician with appropriate medical monitoring and support measures.

Administration

Sub-Q Administration

Administer by sub-Q injection only.

Do not use 80 mg/0.8 mL concentration in pediatric patients weighing <40 kg. Systemic exposure of asfotase alfa achieved with this concentration is lower than that associated with other strength vials and may provide inadequate efficacy in such patients.

Asfotase alfa injection will appear clear, slightly opalescent or opalescent, and colorless to slightly yellow, possibly with a few small translucent or white particles; discard solutions not consistent with this appearance.

Remove unopened vials of asfotase alfa from refrigeration 15 to 30 minutes before injecting to allow for medication to reach room temperature; do not warm in any other manner. Administer within 3 hours after removing vial(s) from refrigeration.

Vials contain no preservatives and are for single use only; discard any unused solution.

Administer using disposable 1-mL syringes and ½-inch, 25- to 29-gauge needles; use new syringe and needle for each injection. Use of 2 different gauge needles is recommended— larger bore (e.g., 25 gauge) needle for medication withdrawal and smaller bore (e.g., 29 gauge) needle for injection.

To reduce risk of lipodystrophy, rotate injection sites at the abdominal, thigh, deltoid, and buttock areas. Do not inject into areas that are reddened, inflamed, or swollen.

Dosage

Dosage based on patient weight. Round patient's weight to the nearest kg when determining asfotase alfa dosage.

Round calculated total injection volume to nearest 0.01 mL. When total injection volume >1 mL, divide volume equally into 2 syringes; administer at separate injection sites.

For more detailed information on weight-based dosage of this drug by treatment regimen as well as required volume of injection and concentration/number of vials, consult dosage tables in the manufacturer's labeling.

Pediatric Patients

Hypophosphatasia

Perinatal/Infantile-onset Hypophosphatasia

Sub-Q

6 mg/kg weekly (as either 2 mg/kg 3 times weekly or 1 mg/kg 6 times weekly).

Injection site reactions may limit tolerability of 6-times-weekly regimen.

Dosage may be increased up to 9 mg/kg weekly (as 3 mg/kg three times weekly) for lack of efficacy (e.g., no improvement in respiratory status, growth, or radiographic findings).

Juvenile-onset Hypophosphatasia

Sub-Q

6 mg/kg weekly (as 2 mg/kg 3 times weekly or 1 mg/kg 6 times weekly).

Injection site reactions may limit tolerability of 6-times-weekly regimen.

Special Populations

No special population dosage recommendations for geriatric patients or those with hepatic or renal impairment at this time.

Cautions for Asfotase Alfa

Contraindications

None.

Warnings/Precautions

Warnings

Hypersensitivity Reactions Including Anaphylaxis

Life-threatening hypersensitivity reactions (e.g., anaphylaxis) reported (see Boxed Warning). Manifestations included difficulty breathing, choking sensation, nausea, periorbital edema, and dizziness. May occur within minutes following injection and in patients receiving therapy for >1 year after treatment initiation.

Anaphylaxis reported during both the early course and after extended duration of asfotase alfa therapy. Initiate asfotase alfa under supervision of a clinician with appropriate medical monitoring and support measures. If a severe hypersensitivity reaction occurs (e.g., anaphylaxis), discontinue asfotase alfa therapy and initiate appropriate treatment, including epinephrine administration. Consider risks and benefits of readministering asfotase alfa following severe hypersensitivity reaction; if readministration occurs, monitor patient for signs and symptoms of a severe hypersensitivity reaction. Inform patients of symptoms of life-threatening hypersensitivity reactions and instruct them to seek immediate medical care if such symptoms occur.

Other Warnings/Precautions

Lipodystrophy

Localized lipodystrophy, including lipoatrophy and lipohypertrophy, reported at injection sites following several months of asfotase alfa therapy.

Advise patients to follow proper injection technique and to rotate injection sites.

Ectopic Calcifications

Ectopic calcification of the eye (including the cornea and conjunctiva) and kidney (nephrocalcinosis, nephrolithiasis) reported in patients with HPP. Reported cases of ectopic calcification were not associated with visual changes or changes in renal function.

Patients with HPP are at increased risk for developing ectopic calcifications. Not known whether ectopic calcifications in patients receiving asfotase alfa were related to the drug or underlying disease state.

Patients should undergo ophthalmologic examinations and renal ultrasound at baseline and periodically during therapy to monitor for signs and symptoms of ectopic calcification and for changes in vision or renal function.

Possible Immune-mediated Clinical Effects

In clinical studies, most patients developed anti-drug and neutralizing antibodies, which resulted in reduced systemic exposure of asfotase alfa. In postmarketing reports, some patients with an initial therapeutic response to asfotase alfa subsequently developed recurrence and worsening in disease-associated laboratory and radiographic biomarkers. Effect of anti-drug antibody formation on the long-term efficacy of asfotase alfa is unknown. If progression or worsening of disease-associated laboratory and imaging biomarkers after an initial therapeutic response occurs, consider obtaining anti-drug antibody testing by contacting Alexion at 1-888-765-4747 or at medinfo@alexion.com. Follow these patients closely.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity with asfotase alfa therapy. In clinical trials of asfotase alfa for HPP, anti-drug antibodies detected in 89% of patients who had post-baseline antibody data; 57% of these patients also showed presence of neutralizing antibodies. No correlation observed between anti-drug antibody titer and neutralizing antibody (percent inhibition) values.

Specific Populations

Pregnancy

No adequate and well-controlled studies in pregnant women.

No evidence of fetotoxicity, embryolethality, or teratogenicity in animals.

Lactation

Not known whether distributed into human milk. Effects of drug on milk production or on breast-fed infant also unknown.

Consider known benefits of breast-feeding along with mother's clinical need for asfotase alfa and any potential effects of drug or disease on the infant.

Pediatric Use

Efficacy and safety established in pediatric patients with perinatal/infantile- and juvenile-onset HPP.

Geriatric Use

No experience in patients ≥65 years of age; not known whether geriatric patients respond differently than younger patients.

Common Adverse Effects

Most common adverse reactions (≥10%) include injection site reactions, lipodystrophy, ectopic calcifications, hypersensitivity reactions.

Drug Interactions

No formal drug-drug interaction studies to date.

Studies revealed analytical interference between asfotase alfa and laboratory tests that utilize an alkaline phosphatase-conjugated test system, which results in incorrect test results in patients administered asfotase alfa. Laboratory assays which do not have alkaline phosphatase-conjugate technology recommended for use when testing samples from patients receiving asfotase alfa. Inform laboratory personnel that a patient is being treated with asfotase alfa and discuss use of a testing platform which does not utilize an alkaline phosphatase-conjugated test system.

Expect elevated levels of serum alkaline phosphatase in patients administered asfotase alfa. Do not rely on serum alkaline phosphatase measurements for clinical decision making in these patients.

Asfotase Alfa Pharmacokinetics

Absorption

Bioavailability

Approximately 62% following sub-Q administration.

Steady-state exposure achieved as early as 3 weeks.

Concentration of asfotase alfa injection affects drug exposure; at same dosage, exposure approximately 25% lower with 100-mg/mL concentration compared with 40-mg/mL concentration.

Time to peak plasma concentrations following multiple sub-Q doses of 2 mg/kg 3 times weekly in patients with HPP approximately 15 or 21 hours in patients ≤5 years of age or those >5 to 12 years of age, respectively.

Pharmacokinetics dose-proportional across dosage range of 0.3–3 mg/kg once every other day (three times weekly).

Formation of anti-drug antibodies reduces systemic exposure of asfotase alfa.

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Half-life

Approximately 5 days.

Stability

Storage

Parenteral

Injection

2–8°C. Protect from light; store in original carton until time of use. Do not freeze or shake.

Actions

Biosynthetic (recombinant DNA origin) form of human TNSALP, a metalloenzyme that catalyzes hydrolysis of phosphomonoesters.
Specific activity of asfotase alfa is 620–1250 units/mg, with 1 unit defined as amount of asfotase alfa that results in formation of 1 µmol of p-nitrophenol from p-nitrophenyl phosphate per minute at 37°C.
Provides exogenous source of TNSALP, reducing accumulation of TNSALP substrates, promoting bone mineralization, and improving skeletal structure.

Advice to Patients

Advise patients and their caregivers to read the manufacturer's patient information and instructions for use.
Instruct patients and/or caregivers regarding proper dosage, preparation, and administration of asfotase alfa, including use of aseptic technique and safe disposal of needles and syringes.
Inform patients of the risk of lipodystrophy and localized atrophy at injection sites. Stress importance of following proper injection technique and rotating injection sites.
When the injection volume exceeds 1 mL, stress importance of dividing the volume equally between 2 syringes and injecting into separate sites.
Inform patients of the risk of injection site reactions and other administration-associated adverse reactions (e.g., erythema, discoloration/hypopigmentation, pain/tenderness, pruritus, swelling, induration, macules, bruising, nodules).
Inform patients of signs and symptoms of life-threatening hypersensitivity reactions, including anaphylaxis, and advise patients to seek immediate medical care if such symptoms occur.
Since anti-drug antibodies may occur during treatment, inform patients or their caregivers to contact their clinician if worsening symptoms of hypophosphatasia (HPP) (e.g., increased respiratory support, increased difficulty walking, new fractures) occur.
Inform patients of the HPP registry established to monitor the variability and progression of HPP and the long-term effects of asfotase alfa ([Web]). Encourage patient participation in this voluntary program and advise patients that participation may involve long-term follow-up.
Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
Advise patients to inform clinicians if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.