1 INDICATIONS AND USAGE LUMIZYME ® is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (acid α-glucosidase [GAA] deficiency).

LUMIZYME ® is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (GAA deficiency).

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6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1) ] The most frequently reported adverse reactions (≥5%) in clinical trials were hypersensitivity reactions and included: anaphylaxis, rash, pyrexia, flushing/feeling hot, urticaria, headache, hyperhidrosis, nausea, cough, decreased oxygen saturation, tachycardia, tachypnea, chest discomfort, dizziness, muscle twitching, agitation, cyanosis, erythema, hypertension/increased blood pressure, pallor, rigors, tremor, vomiting, fatigue, and myalgia.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme at 1-800-633-1610, option 1 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 clinical practice.

In clinical trials, the most common adverse reactions (≥5%) following intravenous alglucosidase alfa treatment were hypersensitivity reactions, and included anaphylaxis, rash, pyrexia, flushing/feeling hot, urticaria, headache, hyperhidrosis, nausea, cough, decreased oxygen saturation, tachycardia, tachypnea, chest discomfort, dizziness, muscle twitching, agitation, cyanosis, erythema, hypertension/increased blood pressure, pallor, rigors, tremor, vomiting, fatigue, and myalgia.

Adverse Reactions in Clinical Trials in Infantile-Onset and Juvenile-Onset Pompe Disease Two multicenter, open-label clinical trials (Trials 1 and 2) [see Clinical Studies (14.1) ] were conducted in 39 patients with infantile-onset Pompe disease (IOPD), aged 1 month to 3.5 years old.

Approximately half of the patients (54%) were male.

Patients were treated with intravenous alglucosidase alfa 20 or 40 mg/kg every other week for periods ranging from 1 to 106 weeks (mean: 61 weeks).

The most serious adverse reactions reported with alglucosidase alfa treatment included anaphylaxis and acute cardiorespiratory failure.

The most common adverse reactions requiring intervention in these clinical trials were hypersensitivity reactions, that occurred in 20 of 39 (51%) patients treated with alglucosidase alfa, and included rash, pyrexia, urticaria, flushing, decreased oxygen saturation, cough, tachypnea, tachycardia, hypertension/increased blood pressure, pallor, rigors, vomiting, cyanosis, agitation, and tremor.

These reactions were more likely to occur with higher infusion rates or doses.

Some patients who were pretreated with antihistamines, antipyretics and/or corticosteroids still experienced hypersensitivity reactions.

Table 2 summarizes all adverse reactions that occurred in ≥5% of patients (2 or more patients) treated with alglucosidase alfa in clinical trials described above.

Table 2: Adverse Reactions that Occurred in at Least 5% of Alglucosidase Alfa-Treated Infantile-Onset Patients in Trials 1 and 2 Number of Patients (N=39) n (%) Adverse Reaction 20 (51) Rash (including rash erythematous, rash macular and maculopapular) 7 (18) Pyrexia 6 (15) Urticaria 5 (13) Flushing 5 (13) Hypertension/Increased Blood Pressure 4 (10) Decreased Oxygen Saturation 3 (8) Cough 3 (8) Tachypnea 3 (8) Tachycardia 3 (8) Erythema 2 (5) Vomiting 2 (5) Rigors 2 (5) Pallor 2 (5) Cyanosis 2 (5) Agitation 2 (5) Tremor 2 (5) An open-label, single-center trial (Trial 3) was conducted in 18 treatment-naive patients with IOPD who were treated with alglucosidase alfa [see Clinical Studies (14.1) ] .

Adverse reactions observed in these patients were similar to patients with IOPD who received alglucosidase alfa in other clinical trials.

Additional hypersensitivity reactions observed in patients with IOPD treated with alglucosidase alfa in other clinical trials and expanded access programs included livedo reticularis, irritability, retching, increased lacrimation, ventricular extrasystoles, nodal rhythm, rales, respiratory tract irritation, and cold sweat.

Safety was also evaluated in 99 patients (51 male, 48 females) with Pompe disease in an ongoing, open-label, prospective study in patients 12 months of age and older who were previously treated with another alglucosidase alfa product and switched to LUMIZYME.

Patients were aged 1 to 18 years with a median duration of treatment of 437 days (range 13 to 466 days).

No new safety findings were observed following the switch to 4000 L scale of alglucosidase alfa.

Adverse Reactions in Clinical Trials in Late-Onset Pompe Disease Assessment of adverse reactions in patients with late-onset Pompe disease (LOPD) is based on the exposure of 90 patients (45 male, 45 female), aged 10 to 70 years, to intravenous infusions of 20 mg/kg alglucosidase alfa or placebo in a randomized, double-blind, placebo-controlled trial (Trial 4).

All patients were naive to enzyme replacement therapy.

Patients were randomized in a 2:1 ratio and received intravenous alglucosidase alfa or placebo every other week for 78 weeks (18 months).

Two patients who received alglucosidase alfa discontinued the trial due to anaphylactic reactions.

Serious adverse reactions reported with alglucosidase alfa included anaphylaxis, which presented as angioedema, throat tightness and chest pain/discomfort.

One patient with a history of Wolff-Parkinson-White syndrome experienced a serious adverse reaction of supraventricular tachycardia.

The most common adverse reactions (≥3%; 2 or more patients) observed in alglucosidase alfa-treated patients were hypersensitivity reactions and included anaphylaxis, headache, nausea, urticaria, dizziness, chest discomfort, vomiting, hyperhidrosis, flushing/feeling hot, increased blood pressure, paresthesia, pyrexia, local swelling, diarrhea, pruritus, rash, and throat tightness.

Delayed-onset reactions, defined as adverse reactions that occurred 2 to 48 hours after completion of alglucosidase alfa infusion, that were observed in ≥3% more patients in the alglucosidase alfa-treated group compared to patients in the placebo-treated group in the controlled trial, included hyperhidrosis.

Additional delayed-onset reactions that occurred in alglucosidase alfa-treated patients included fatigue, myalgia, and nausea.

Table 3 summarizes the most common adverse reactions that occurred in at least 3% of alglucosidase alfa-treated patients and with a higher incidence than the placebo-treated patients in Trial 4 (patients with LOPD).

Table 3: Adverse Reactions in Patients with LOPD (Trial 4) Adverse reactions that occurred in ≥3% of alglucosidase alfa-treated patients and with a higher incidence than placebo-treated patients Adverse Reaction Alglucosidase Alfa n=60 N (%) Placebo n=30 N (%) Hyperhidrosis 5 (8.3) 0 (0) Urticaria 5 (8.3) 0 (0) Anaphylaxis 4 (6.7) 0 (0) Chest Discomfort 4 (6.7) 1 (3.3) Muscle Twitching 4 (6.7) 1 (3.3) Myalgia 3 (5.0) 1 (3.3) Flushing/Feeling Hot 3 (5.0) 0 (0) Increased Blood Pressure 3 (5.0) 0 (0) Vomiting 3 (5.0) 0 (0) Edema, Peripheral 2 (3.3) 0 (0) Pruritus 2 (3.3) 0 (0) Rash Papular 2 (3.3) 0 (0) Throat Tightness 2 (3.3) 0 (0) 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of alglucosidase alfa.

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.

In the postmarketing experience with LUMIZYME, serious adverse reactions have been reported, including anaphylaxis [see Boxed Warning and Warnings and Precautions (5.1) ] .

Acute cardiorespiratory failure, possibly associated with fluid overload, has been reported in infantile-onset Pompe disease patients with pre-existing hypertrophic cardiomyopathy [see Boxed Warning and Warning and Precautions (5.3) ] .

Infusion associated reactions, including pyrexia, chills, fatigue, urticaria, rash, pruritus, erythema, dyspnea, hypotension, bradycardia, tachycardia, flushing, nausea, headache, and syncope have been reported with alglucosidase alfa.

In addition to the hypersensitivity reactions reported in clinical trials [see Adverse Reactions (6.1) ] , the following hypersensitivity reactions have been reported in at least 2 patients and included: anaphylactic shock, respiratory failure, respiratory arrest, cardiac arrest, hypoxia, dyspnea, wheezing, convulsions, peripheral coldness, restlessness, nervousness, back pain, stridor, pharyngeal edema, abdominal pain, apnea, muscle spasm, and conjunctivitis.

In addition, one case of hyperparathyroidism has been reported.

Systemic and cutaneous immune-mediated reactions, including proteinuria and nephrotic syndrome secondary to membranous glomerulonephritis, and necrotizing skin lesions have been reported in postmarketing safety experience with alglucosidase alfa [see Warnings and Precautions (5.2) ] .