). Infusion reactions which were reported in ≥ 5% of Myozyme -treated late-onset patients included headache, nausea, urticaria, dizziness, chest discomfort, hyperhidrosis, flushing, blood pressure increased, and vomiting. Serious infusion-associated reactions included rales, bronchospasm, oxygen saturation decreased, tachypnea, tachycardia, periorbital edema, urticaria, hypertension, heart rate increased and fever.
Most infusion-associated reactions requiring intervention were ameliorated with slowing the infusion rate, temporarily stopping the infusion and/or administration of antipyretics, antihistamines or corticosteroids. All patients recovered without sequelae from the reactions.
) at the time of Myozyme infusion appear to be at greater risk for infusion-associated reactions. Careful consideration should be given to the patient’s clinical status prior to administration of Myozyme (see 7 WARNINGS AND PRECAUTIONS).
Infusion reactions are also more likely to occur with higher infusion rates. Patients with advanced Pompe’s Disease may have compromised cardiac and respiratory function, which may also predispose them to a higher risk of severe complications from infusion reactions.
In clinical trials, some patients were pre-treated with antihistamines, antipyretics and/or Myozyme (alglucosidase alfa for injection) Page 11 of 46 Protected B / Protégé B corticosteroids. Infusion reactions occurred in some patients after receiving antipyretics, antihistamines and/or corticosteroids.
Patients should be closely monitored during the Myozyme infusion. Infusion reactions may occur at any time during, or shortly after completion of Myozyme infusion. If the patient experiences an infusion reaction during the Myozyme infusion, the patient should be managed according to general standards of care consistent with treatment of the presenting symptom(s).
Regardless of pre- treatment, reduction of the infusion rate, temporarily interrupting the infusion, and/or administration of antihistamines, antipyretics and/or corticosteroids may ameliorate the symptoms. If severe infusion reactions occur, immediate discontinuation of the Myozyme infusion should be considered, and appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be available.
Severe infusion reactions are generally managed with administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In sosme cases of anaphylactic reactions epinephrine was administered.
Patients who have experienced infusion reactions should be treated with caution when they are readministered Myozyme. Immunogenicity The effect of IgG antibody formation on safety and efficacy has been evaluated in clinical trials and post-marketing experience.
In clinical studies, the majority of patients developed IgG antibodies to alglucosidase alfa and seroconversion typically occurred within 3 months of treatment. Thus seroconversion is expected to occur in most patients treated with Myozyme.
Overall, a correlation was not observed between the onset of IARs and the time of IgG antibody formation. IARs can occur across all levels of antibody titres, however a trend was observed for more frequent IARs with higher titres of IgG antibody.
The development of high and sustained IgG antibody titres is one of several factors that may contribute to diminished clinical efficacy. With regard to IOPD, a tendency was observed for patients treated with a higher dose (40 mg/kg) to develop higher titres of IgG antibodies.
Furthermore, Cross Reactive Immunologic Material (CRIM) status has been shown to be associated with immunogenicity and patients’ responses to enzyme replacement therapies. Negative CRIM status, indicating no endogenous enzyme is detected, is a risk factor to develop high and sustained IgG antibody titres.
This risk is higher among CRIM negative patients versus CRIM-positive patients and is a contributing factor to reduced clinical efficacy. However, high and sustained IgG antibody titres has also occurred in a limited number of CRIM-positive patients, generally with very low endogenous enzyme.
With respect to LOPD patients, the majority showed either stabilizing or decreasing antibody titres over time. The development of high and sustained IgG antibody titres is infrequent in LOPD patients. Thus, the impact of IgG antibodies is more limited for LOPD patients.
Some IgG positive infantile-onset and late-onset patients in clinical trials who were retrospectively evaluated for the presence of inhibitory antibodies tested positive for inhibition of enzyme activity and/or uptake in in vitro assays.
However, the clinical relevance of this in vitro inhibition is unclear (see 8 ADVERSE REACTIONS, Clinical Trial Adverse Drug Reactions, Infantile-Onset Disease, Immunogenicity; Late-Onset Disease, Immunogenicity sections). IgG antibody titres should be monitored based on clinical phenotype.
Baseline serum sample collection prior to the first infusion is strongly encouraged. For IOPD patients, regular monitoring during first year of treatment (example: every 3 months) is suggested and subsequent monitoring depending on clinical Myozyme (alglucosidase alfa for injection) Page 12 of 46 Protected B / Protégé B outcomes and antibody titres level.
For LOPD patients, antibody development should be assessed within 6 months and subsequent monitoring as clinically warranted based on safety and efficacy considerations. A small number of patients who were evaluated tested positive for alglucosidase alfa-specific IgE antibodies, some of whom experienced anaphylactic reactions.
Testing was typically performed for IARs suggestive of hypersensitivity reactions. Some patients have been successfully rechallenged using slower […]