ADVERSE REACTIONS
The most frequent serious adverse events related to the use of NAGLAZYME occurred during infusions and included urticaria of the face and neck, bronchospasm, respiratory distress, and apnea (see
WARNINGS: Infusion Reactions).
The most common adverse reactions observed in the clinical studies were headache, fever, arthralgia, vomiting, upper respiratory infections, abdominal pain, diarrhea, ear pain, cough, and otitis media.
The most common adverse reactions requiring interventions were infusion-related reactions (see
WARNINGS: Infusion Reactions).
Because clinical trials are conducted under widely varying conditions, the observed adverse reaction rates may not predict the rates observed in patients in clinical practice.
Table 3 enumerates adverse events that were reported during the 6-month placebo-controlled trial and occurred in at least 2 patients more in the NAGLAZYME group than in the placebo group. Observed adverse events in the Phase 1, Phase 2, and open-label extension studies were not different in nature or severity.
Table 3: Number and Percentage of Patients with Selected Adverse Events in the Placebo-Controlled Study
| Adverse Event |
NAGLAZYME (n = 19) |
Placebo (n = 20) |
| No. Patients (%) |
No. Patients (%) |
| All |
19 (100) |
20 (100) |
| Abdominal Pain |
10(53) |
6 (30) |
| Ear Pain |
8 (42) |
4 (20) |
| Pain |
5 (26) |
1 (5) |
| Conjunctivitis |
4 (21) |
0 |
| Dyspnea |
4 (21) |
2 (10) |
| Rigors |
4 (21) |
0 |
| Chest Pain |
3 (16) |
1 (5) |
| Pharyngitis |
3 (16) |
1 (5) |
| Areflexia |
2 (11) |
0 |
| Increased Corneal Opacity |
2 (11) |
0 |
| Face Edema |
2 (11) |
0 |
| Gastroenteritis |
2 (11) |
0 |
| Hypertension |
2 (11) |
0 |
| Malaise |
2 (11) |
0 |
| Nasal Congestion |
2 (11) |
0 |
| Umbilical Hernia |
2 (11) |
0 |
Immunogenicity
Ninety-eight percent (53/54) of all patients treated with NAGLAZYME developed anti-galsulfase IgG antibodies. Initial evidence of antibody development typically appeared following 4 to 8 weeks of treatment. No association was observed between antibody development and urinary GAG levels.
Five patients with high antibody levels had observable differences in pharmacokinetic parameters (see
CLINICAL PHARMACOLOGY: Pharmacokinetics). Antibodies from one patient were analyzed for neutralizing effect and showed evidence of in vitro inhibition of galsulfase activity. Because only one patient sample was analyzed for neutralizing activity, the effects of neutralizing antibodies are unclear.
The data reflect the percentage of patients whose test results were considered positive for antibodies to galsulfase using an enzyme-linked immunosorbent assay (ELISA) for galsulfase-specific IgG-binding antibodies, and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibodies in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to galsulfase with the incidence of antibodies to other products may be misleading.
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