STRENSIQ SIDE EFFECTS
- Generic Name: asfotase alfa for subcutaneous administration
- Brand Name: Strensiq
- Drug Class: Enzymes, Metabolic
SIDE EFFECTS
The following adverse reactions are described below and elsewhere in the labeling:
- Hypersensitivity Reactions
- Lipodystrophy
- Ectopic Calcifications
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.
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 1 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 1: Adverse Reactions Reported in at Least 10% of Patients with Perinatal/Infantile-or Juvenile-onset HPP Enrolled in STRENSIQ Clinical Trials
| Adverse Reaction Category or Term | Perinatal/ Infantile-onset HPP | Juvenile-onset HPP (N=20) n (%) |
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| STRENSIQ less than or equal to 6 mg/kg per week (N=66) n (%) |
STRENSIQ more than 6 mg/kg/weeka (N=13) n (%) |
Total (N=79) n (%) |
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| 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 reactionsb | 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 lipodystrophyc | 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 reactionsd | 6 (9) | 2 (15) | 8 (10) | 2 (10) |
| a 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). b Other injection site reactions include injection site rash, inflammation, papule, hemorrhage, hematoma, urticaria, warmth, calcification, mass, scar and cellulitis. c Other lipodystrophy includes lipohypertrophy. d Other hypersensitivity reactions include erythema/redness, pyrexia/fever, irritability, nausea, pain, rigor/chills, hypoesthesia oral, headache, flushing, and anaphylaxis. |
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Less Common Adverse Reactions
Adverse reactions that occurred at rates less than 1% included:
- Hypocalcemia
- Renal stones
- Chronic hepatitis
- Decreased vitamin B6
Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. During clinical trials, anti-drug 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 98 patients with hypophosphatasia (HPP) enrolled in the clinical trials and who had post-baseline antibody data, 76 (78%) tested positive for anti-drug antibodies at some time point after receiving STRENSIQ treatment. Among those 76 patients, 34 (45%) also showed the presence of neutralizing antibodies. No correlation was observed between the anti-drug antibody titer and neutralizing antibody (% inhibition) values. Formation of anti-drug antibody resulted in a reduced systemic exposure of asfotase alfa.
The detection of antibody formation is 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 to STRENSIQ with the incidence of antibodies to other products may be misleading.
SRC: NLM .