STRENSIQ
Generic: ASFOTASE ALFA
Basic Information
Manufacturer
Alexion Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
3387574f-5eaa-4501-a71d-4cbfbd563031
Indications & Usage
1 INDICATIONS AND USAGE STRENSIQ ® is indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).
STRENSIQ is a tissue nonspecific alkaline phosphatase indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).
( 1 )
STRENSIQ is a tissue nonspecific alkaline phosphatase indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Lipodystrophy [see Warnings and Precautions (5.2) ] Ectopic Calcifications [see Warnings and Precautions (5.3) ] Possible Immune-Mediated Clinical Effects [see Warnings and Precautions (5.4) ] Most common adverse reactions (≥ 10%) are injection site reactions, lipodystrophy, ectopic calcifications and hypersensitivity reactions.
( 6.1 ) 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.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below 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 [see Clinical Studies (14) ] .
Common Adverse Reactions Overall, the most common adverse reactions reported were injection site reactions (63%) .
Other common adverse reactions included lipodystrophy (28%), ectopic calcifications (14%), and hypersensitivity reactions (12%).
Table 4 summarizes the adverse reactions that occurred at a rate of at least 10% in clinical trials following subcutaneous injection of STRENSIQ by patient population and STRENSIQ dosage regimen.
The frequency of injection site reactions, lipodystrophy and ectopic calcification were higher in patients with juvenile-onset HPP as compared to perinatal/infantile-onset HPP patients.
The majority of injection site reactions resolved within a week.
Two patients experienced injection site reactions that led to reductions of their STRENSIQ dose.
One patient switched from six times per week dosing to 3 times per week dosing as a result of injection site reactions.
One other patient experienced a severe injection site reaction of injection site discoloration and withdrew from the trial.
Table 4: Adverse Reactions Reported in at Least 10% of Patients with Perinatal/Infantile- or Juvenile-onset HPP Enrolled in STRENSIQ Clinical Trials Perinatal/Infantile-onset HPP Juvenile-onset HPP Adverse Reaction Category or Term STRENSIQ less than or equal to 6 mg/kg per week (N=66) n (%) STRENSIQ more than 6 mg/kg/week Adverse reactions are from the combined period of 6 mg/kg and above (i.e.
total drug exposure regardless of starting dose and intermediary doses as long as the patient reached doses > 6 mg/kg) (N=13) n (%) 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 reactions Other injection site reactions include injection site rash, inflammation, papule, hemorrhage, hematoma, urticaria, warmth, calcification, mass, scar and cellulitis.
10 (15) 3 (23) 13 (17) 4 (20) Ectopic calcifications 3 (5) 0 (0) 3 (4) 11 (55) Lipodystrophy 12 (18) 2 (15) 14 (18) 14 (70) Injection site atrophy 4 (6) 2 (15) 6 (8) 8 (40) Injection site hypertrophy 5 (8) 0 (0) 5 (6) 6 (30) Other lipodystrophy Other lipodystrophy includes lipohypertrophy.
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 reactions Other hypersensitivity reactions include erythema/redness, pyrexia/fever, irritability, nausea, pain, rigor/chills, hypoesthesia oral, headache, flushing, and anaphylaxis.
6 (9) 2 (15) 8 (10) 2 (10) Less Common Adverse Reactions Adverse reactions that occurred at rates less than 1% included: Hypocalcemia Renal Stones Chronic hepatitis Decreased vitamin B6 Long-Term Safety In long-term extension trials reflecting a median exposure to STRENSIQ of 142 weeks (range 0.1 weeks to 392 weeks) in 112 patients with perinatal/infantile- (n = 89), juvenile- (n = 22), and adult-onset (n = 1) HPP (age at enrollment = 1 day to 66.5 years), the most common adverse reactions were similar to those reported in Table 4.
6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of the antibodies in the studies described below with the incidence of antibodies in other studies or to other asfotase alfa products may be misleading.
During clinical trials, anti-asfotase alfa antibodies have been detected in patients receiving treatment with STRENSIQ using an electrochemiluminescent (ECL) immunoassay.
Antibody positive samples were tested to determine the presence of neutralizing antibodies based on in vitro inhibition of the catalytic activity of STRENSIQ.
Among STRENSIQ-treated patients with hypophosphatasia (HPP) in clinical studies who had post-baseline antibody data available, 97/109 (89%) tested positive for anti-asfotase alfa antibodies at some time point during STRENSIQ treatment.
Among those 97 patients, 55 (57%) also tested positive for neutralizing antibodies at some time point during STRENSIQ treatment.
No correlation was observed between the anti-asfotase alfa antibody titers and the neutralizing antibody (% inhibition) values.
Formation of anti-asfotase alfa antibody resulted in a reduced systemic exposure of asfotase alfa [see Clinical Pharmacology (12.3) ] .
6.3 Postmarketing Experience The following adverse reactions have been identified during post-approval use of STRENSIQ.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Some STRENSIQ-treated patients with initial therapeutic response to STRENSIQ subsequently developed 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 [see Warnings and Precautions (5.4) ].
( 6.1 ) 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.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below 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 [see Clinical Studies (14) ] .
Common Adverse Reactions Overall, the most common adverse reactions reported were injection site reactions (63%) .
Other common adverse reactions included lipodystrophy (28%), ectopic calcifications (14%), and hypersensitivity reactions (12%).
Table 4 summarizes the adverse reactions that occurred at a rate of at least 10% in clinical trials following subcutaneous injection of STRENSIQ by patient population and STRENSIQ dosage regimen.
The frequency of injection site reactions, lipodystrophy and ectopic calcification were higher in patients with juvenile-onset HPP as compared to perinatal/infantile-onset HPP patients.
The majority of injection site reactions resolved within a week.
Two patients experienced injection site reactions that led to reductions of their STRENSIQ dose.
One patient switched from six times per week dosing to 3 times per week dosing as a result of injection site reactions.
One other patient experienced a severe injection site reaction of injection site discoloration and withdrew from the trial.
Table 4: Adverse Reactions Reported in at Least 10% of Patients with Perinatal/Infantile- or Juvenile-onset HPP Enrolled in STRENSIQ Clinical Trials Perinatal/Infantile-onset HPP Juvenile-onset HPP Adverse Reaction Category or Term STRENSIQ less than or equal to 6 mg/kg per week (N=66) n (%) STRENSIQ more than 6 mg/kg/week Adverse reactions are from the combined period of 6 mg/kg and above (i.e.
total drug exposure regardless of starting dose and intermediary doses as long as the patient reached doses > 6 mg/kg) (N=13) n (%) 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 reactions Other injection site reactions include injection site rash, inflammation, papule, hemorrhage, hematoma, urticaria, warmth, calcification, mass, scar and cellulitis.
10 (15) 3 (23) 13 (17) 4 (20) Ectopic calcifications 3 (5) 0 (0) 3 (4) 11 (55) Lipodystrophy 12 (18) 2 (15) 14 (18) 14 (70) Injection site atrophy 4 (6) 2 (15) 6 (8) 8 (40) Injection site hypertrophy 5 (8) 0 (0) 5 (6) 6 (30) Other lipodystrophy Other lipodystrophy includes lipohypertrophy.
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 reactions Other hypersensitivity reactions include erythema/redness, pyrexia/fever, irritability, nausea, pain, rigor/chills, hypoesthesia oral, headache, flushing, and anaphylaxis.
6 (9) 2 (15) 8 (10) 2 (10) Less Common Adverse Reactions Adverse reactions that occurred at rates less than 1% included: Hypocalcemia Renal Stones Chronic hepatitis Decreased vitamin B6 Long-Term Safety In long-term extension trials reflecting a median exposure to STRENSIQ of 142 weeks (range 0.1 weeks to 392 weeks) in 112 patients with perinatal/infantile- (n = 89), juvenile- (n = 22), and adult-onset (n = 1) HPP (age at enrollment = 1 day to 66.5 years), the most common adverse reactions were similar to those reported in Table 4.
6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of the antibodies in the studies described below with the incidence of antibodies in other studies or to other asfotase alfa products may be misleading.
During clinical trials, anti-asfotase alfa antibodies have been detected in patients receiving treatment with STRENSIQ using an electrochemiluminescent (ECL) immunoassay.
Antibody positive samples were tested to determine the presence of neutralizing antibodies based on in vitro inhibition of the catalytic activity of STRENSIQ.
Among STRENSIQ-treated patients with hypophosphatasia (HPP) in clinical studies who had post-baseline antibody data available, 97/109 (89%) tested positive for anti-asfotase alfa antibodies at some time point during STRENSIQ treatment.
Among those 97 patients, 55 (57%) also tested positive for neutralizing antibodies at some time point during STRENSIQ treatment.
No correlation was observed between the anti-asfotase alfa antibody titers and the neutralizing antibody (% inhibition) values.
Formation of anti-asfotase alfa antibody resulted in a reduced systemic exposure of asfotase alfa [see Clinical Pharmacology (12.3) ] .
6.3 Postmarketing Experience The following adverse reactions have been identified during post-approval use of STRENSIQ.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Some STRENSIQ-treated patients with initial therapeutic response to STRENSIQ subsequently developed 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 [see Warnings and Precautions (5.4) ].