Myozyme is indicated for long-term enzyme replacement therapy (ERT) in patients with a confirmed
diagnosis of Pompe disease (acid α-glucosidase deficiency).
Myozyme is indicated in adults and paediatric patients of all ages.

Myozyme treatment should be supervised by a physician experienced in the management of patients
with Pompe disease or other inherited metabolic or neuromuscular diseases.
Posology
The recommended dose regimen of alglucosidase alfa is 20 mg/kg of body weight administered once
every 2 weeks.
Patient response to treatment should be routinely evaluated based on a comprehensive evaluation of
all clinical manifestations of the disease.
Paediatric and older people
There is no evidence for special considerations when Myozyme is administered to paediatric patients
of all ages or older people.
Patients with renal and hepatic impairment
The safety and efficacy of Myozyme in patients with renal or hepatic impairment have not been
evaluated and no specific dose regimen can be recommended for these patients.

Method of administration
Myozyme should be administered as an intravenous infusion.
Infusions should be administered incrementally. It is recommended that the infusion begin at an initial
rate of 1 mg/kg/h and be gradually increased by 2 mg/kg/h every 30 minutes if there are no signs of
infusion associated reactions (IARs) until a maximum rate of 7 mg/kg/h is reached. IARs are
described in section 4.8.
For instructions on reconstitution and dilution of the medicinal product before administration, see
section 6.6.

Hypersensitivity/Anaphylactic reactions
Serious and life-threatening anaphylactic reactions, including anaphylactic shock, have been reported
in infantile- and late-onset patients during Myozyme infusions (see section 4.8). Because of the
potential for severe infusion associated reactions, appropriate medical support measures, including
cardiopulmonary resuscitation equipment, should be readily available when Myozyme is
administered. If severe hypersensitivity or anaphylactic reactions occur, immediate discontinuation of
Myozyme infusion should be considered and appropriate medical treatment should be initiated. The
current medical standards for emergency treatment of anaphylactic reactions are to be observed.
Infusion Associated Reactions
Approximately half of the patients treated with Myozyme in infantile-onset clinical studies and 28%
of the patients treated with Myozyme in a late-onset clinical study developed infusion associated
reactions (IARs). IARs are defined as any related adverse event occurring during the infusion or
during the hours following infusion. Some reactions were severe (see section 4.8). A tendency was
observed in infantile patients treated with a higher dose (40 mg/kg) to experience more symptoms
when developing IARs. Infantile onset patients who develop high IgG antibody titres appear to be at
higher risk for developing more frequent IARs. Patients with an acute illness (e.g. pneumonia, sepsis)
at the time of Myozyme infusion appear to be at greater risk for IARs. Careful consideration should be
given to the patient’s clinical status prior to administration of Myozyme. Patients should be closely
monitored and all cases of IARs, delayed reactions and possible immunological reactions should be
reported to the marketing authorisation holder.
Patients who have experienced IARs (and in particular anaphylactic reactions) should be treated with
caution when re-administering Myozyme (see sections 4.3 and 4.8). Mild and transient effects may
not require medical treatment or discontinuation of the infusion. Reduction of the infusion rate,
temporary interruption of the infusion, or pre-treatment, generally with oral antihistamine and/or
antipyretics and/or corticosteroids, has effectively managed most reactions. IARs may occur at any
time during the infusion of Myozyme or generally up to 2 hours after, and are more likely with higher
infusion rates.
Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which
may predispose them to a higher risk of severe complications from infusion associated reactions.
Therefore, these patients should be monitored more closely during administration of Myozyme.
Immunogenicity
In clinical studies, the majority of patients developed IgG antibodies to alglucosidase alfa typically
within 3 months of treatment. Thus seroconversion is expected to occur in most patients treated with
Myozyme. A tendency was observed for infantile-onset patients treated with a higher dose (40 mg/kg)

to develop higher titres of IgG antibodies. There does not appear to be a correlation between the onset
of IARs and the time of IgG antibody formation. A limited number of the IgG positive patients
evaluated tested positive for inhibitory effects on in vitro testing. Due to the rarity of the condition
and the limited experience to date, the effect of IgG antibody formation on safety and efficacy is
currently not fully established. The probability of a poor outcome and of developing high and
sustained IgG antibody titres appears higher among CRIM-negative patients (Cross Reactive
Immunologic Material; patients in whom no endogenous GAA protein was detected by Western blot
analysis) than among CRIM-positive patients (patients in whom endogenous GAA protein was
detected by Western blot analysis). However, high and sustained IgG antibody titres also occur in
some CRIM-positive patients. The cause of a poor clinical outcome and of developing high and
sustained IgG antibody titres is thought to be multi-factorial. IgG antibody titres should be regularly
monitored.
Patients who experience hypersensitivity reactions may also be tested for IgE antibodies to
alglucosidase alfa and other mediators of anaphylaxis. Patients who develop IgE antibodies to
alglucosidase alfa appear to be at a higher risk for the occurrence of IARs when Myozyme is readministered
(see section 4.8). Therefore, these patients should be monitored more closely during
administration of Myozyme. Some IgE positive patients were successfully rechallenged with
Myozyme using a slower infusion rate at lower initial doses and have continued to receive Myozyme
under close clinical supervision.
Immune-mediated reactions
Severe cutaneous reactions, possibly immune mediated, have been reported with alglucosidase alfa,
including ulcerative and necrotizing skin lesions (see section 4.8). Nephrotic syndrome was observed
in a few Pompe patients treated with alglucosidase alfa and who had high IgG antibody titres (≥
102,400) (see section 4.8). In these patients renal biopsy showed immune complex deposition.
Patients improved following treatment interruption. It is therefore recommended to perform periodic
urinalysis among patients with high IgG antibody titres.
Patients should be monitored for signs and symptoms of systemic immune-mediated reactions
involving skin and other organs while receiving alglucosidase alfa. If immune-mediated reactions
occur, discontinuation of the administration of alglucosidase alfa should be considered and
appropriate medical treatment initiated. The risks and benefits of re-administering alglucosidase alfa
following an immune-mediated reaction should be considered. Some patients have been successfully
rechallenged and continued to receive alglucosidase alfa under close clinical supervision.
Immunomodulation
Patients with Pompe disease are at risk of respiratory infections due to the progressive effects of the
disease on the respiratory muscles. Immunosuppressive agents have been administered in
experimental settings in a small number of patients, in an attempt to reduce or prevent the
development of antibodies to alglucosidase alfa. Fatal and life-threatening respiratory infections have
been observed in some of these patients. Therefore, treating patients with Pompe disease with
immunosuppressive agents may further increase the risk of developing severe respiratory infections
and vigilance is recommended.

No interactions studies have been performed. Because it is a recombinant human protein,
alglucosidase alfa is an unlikely candidate for cytochrome P450 mediated drug-drug interactions.

Pregnancy
There are no data from the use of alglucosidase alfa in pregnant women. Studies in animals have
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Myozyme
should not be used during pregnancy unless clearly necessary.

Breast-feeding
Alglucosidase alfa may be excreted in breast milk. Because there are no data available on effects in
neonates exposed to alglucosidase alfa via breast milk, it is recommended to stop breast-feeding when
Myozyme is used.
Fertility
There are no clinical data on the effects of alglucosidase alfa on fertility. Preclinical data did not
reveal any significant adverse findings (see section 5.3).

No studies on the effects on the ability to drive and use machines have been performed. Because
dizziness has been reported as an infusion associated reaction, this may affect the ability to drive and
use machines on the day of the infusion.

Summary of the safety profile
Infantile-onset Pompe disease
In clinical trials, 39 infantile-onset patients were treated with Myozyme for more than three years
(168 weeks with a median of 121 weeks; see section 5.1). Adverse reactions reported in at least
2 patients are listed in Table 1 by System Organ Class. Adverse reactions were mostly mild to
moderate in intensity and almost all occurred during the infusion or during the 2 hours following the
infusion (infusion associated reactions, IARs). Serious infusion reactions including urticaria, rales,
tachycardia, decreased oxygen saturation, bronchospasm, tachypnea, periorbital edema and
hypertension have been reported.
Late-onset Pompe disease
In a placebo-controlled study lasting 78 weeks, 90 patients with late-onset Pompe disease, aged 10 to
70 years, were treated with Myozyme or placebo randomized in a 2:1 ratio (see section 5.1). Overall,
the numbers of patients experiencing adverse reactions and serious adverse reactions were comparable
between the two groups. The most common adverse reactions observed were IARs. Slightly more
patients in the Myozyme group than in the placebo group experienced IARs (28% versus 23%). The
majority of these reactions were non-serious, mild to moderate in intensity and resolved
spontaneously. Adverse reactions reported in at least 2 patients are listed in Table 1. Serious adverse
reactions reported in 4 patients treated with Myozyme were: angioedema, chest discomfort, throat
tightness, non-cardiac chest pain and supraventricular tachycardia. Reactions in 2 of these patients
were IgE-mediated hypersensitivity reactions.
Tabulated list of adverse reactions
Table 1: Adverse reactions (reported in at least 2 patients) and adverse reactions reported in postmarketing
setting, expanded access programs and non-controlled clinical trials, per System Organ
Class, presented by frequency categories: very common (≥1/10), common (≥1/100 to<1/10),
uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known
(cannot be estimated from the available data). Due to the small patient population, an adverse reaction
reported in 2 patients is classified as common. Within each frequency grouping, adverse reactions are
presented in order of decreasing seriousness.

Description of selected adverse reactions

A small number of patients (<1%) in clinical trials and in the commercial setting developed
anaphylactic shock and/or cardiac arrest during Myozyme infusion that required life-support
measures. Reactions generally occurred shortly after initiation of the infusion. Patients presented with
a constellation of signs and symptoms, primarily respiratory, cardiovascular, edematous and/or
cutaneous in nature (see section 4.4).
Recurrent reactions consisting of flu-like illness or a combination of events such as fever, chills,
myalgia, arthralgia, pain, or fatigue occurring post-infusion and lasting usually for a few days, have
been observed in some patients treated with alglucosidase alfa. The majority of patients were
successfully re-challenged with alglucosidase alfa using lower doses and/or pretreatment with antiinflammatory
drugs and/or corticosteroids and have continued to receive treatment under close
clinical supervision.
Patients with moderate to severe or recurrent IARs have been evaluated for alglucosidase alfa specific
IgE antibodies; some patients tested positive including some who experienced an anaphylactic
reaction.
Nephrotic syndrome as well as severe cutaneous reactions, possibly immune mediated, have been
reported with alglucosidase alfa including ulcerative and necrotizing skin lesions (see section 4.4).

Reporting of suspected adverse reactions:
Saudi Arabia: The National Pharmacovigilance and Drug Safety Centre (NPC)Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Exts: 2317-2356-2340. reporting hotline : 19999
E-mail: npc.drug@sfda.gov.sa Website: www.sfda.gov.sa/npc
Sanofi- Pharmacovigilance: KSA_Pharmacovigilance@sanofi.com

There is no experience with overdose of alglucosidase alfa. In clinical studies doses up to 40 mg/kg
body weight were used.

Pharmacotherapeutic group: Other alimentary tract and metabolism products, enzymes.
ATC code: A16AB07.
Pompe disease
Pompe disease is a rare, progressive and fatal metabolic myopathy with an estimated global incidence
of 1 in 40,000 births. Other names for Pompe disease include glycogen storage disease type II (GSDII),
acid maltase deficiency (AMD) and glycogenosis type II. Pompe disease belongs to the lysosomal
storage disorders as it is caused by a deficiency of a naturally-occurring lysosomal hydrolase, acid α-
glucosidase (GAA) that degrades lysosomal glycogen to glucose. Deficiency of this enzyme leads to
glycogen accumulation in various tissues, particularly cardiac, respiratory and skeletal muscle, leading
to the development of hypertrophic cardiomyopathy and progressive muscle weakness, including
impairment of respiratory function.
The clinical presentation of Pompe disease can be described as a spectrum of disease which ranges
from a rapidly-progressing infantile-onset form (onset of symptoms of Pompe disease typically within
the first year of life and a very short expected life-span) to a less rapidly-progressing late-onset form.

The infantile-onset form of Pompe disease is characterised by massive deposition of glycogen in the
heart, and skeletal muscle always resulting in rapidly progressive cardiomyopathy, generalised muscle
weakness and hypotonia. Motor development is often completely arrested, or if motor milestones are
achieved, they are subsequently lost. Death typically occurs due to cardiac and/or respiratory failure
before the age of one year.
In a retrospective natural history study in patients with infantile-onset Pompe disease (n=168), the
median age at onset of symptoms was 2.0 months and the median age of death was 9.0 months.
Kaplan-Meier survival rates at 12, 24 and 36 months of age were 26%, 9% and 7%, respectively.
A non-typical, more slowly progressive form of infantile-onset Pompe disease has been described
which is characterised by a less severe cardiomyopathy and consequently a more prolonged survival.
The late-onset form of Pompe disease manifests during infancy, childhood, adolescence or even
adulthood and is much less rapidly progressive than the infantile-onset form. Usually, it is
characterised by the presence of sufficient residual GAA activity to preclude the development of
cardiomyopathy, however some cardiac involvement has been reported in up to approximately 4% of
patients with late-onset Pompe disease.
Patients with late-onset Pompe disease typically present with progressive myopathy, predominantly of
the proximal muscles in the pelvic and shoulder girdles, and varying degrees of respiratory
involvement, ultimately progressing to profound disability and/or the need for ventilatory support.
The time course of disease progression is extremely variable and not predictable, with some patients
experiencing a rapid deterioration in skeletal and respiratory muscle function leading to loss of
ambulation and respiratory failure, others progressing less rapidly, and yet others presenting with a
dissociation in the progression of skeletal and respiratory muscle involvement.
Mechanism of action
It is postulated that Myozyme will restore lysosomal GAA activity resulting in stabilisation or
restoration of cardiac and skeletal muscle function (including respiratory muscles). Due to the bloodbrain
barrier effect and the enzyme’s size, uptake of alglucosidase alfa in the central nervous system is
unlikely.
Clinical efficacy and safety
Infantile-onset Pompe disease; clinical trial in patients aged 6 months or less
The safety and efficacy of Myozyme was assessed in a pivotal, randomised, open-label, historicallycontrolled
clinical trial of 18 non-ventilated infantile-onset patients aged 6 months or less at the onset
of treatment. The untreated historical cohort was matched to the pivotal study population and was
derived from a retrospective natural history study (n=42) in patients with infantile-onset Pompe
disease. Patients were randomized to receive either 20 mg/kg or 40 mg/kg once every two weeks for a
period of 52 weeks. After a minimum of 52 weeks, 16 of these 18 patients were enrolled in an
extension study to receive continued treatment at the same dose for a total duration of up to three
years (150 weeks).
The primary endpoint was the proportion of patients who were alive and free of invasive ventilator
support. However, the invasive ventilator-free survival was not recorded in the untreated historical
cohort and a comparison of this endpoint is not possible. After 52 weeks of treatment, all 18 patients
treated with Myozyme were alive and 15 of these 18 patients were alive and free of invasive
ventilatory support whereas 1 of 42 patients in the untreated historical cohort was alive at 18 months
of age. Two patients died and did not enter into the extension study. After 104 weeks of treatment, all
16 patients who enrolled in the extension study were alive and 10 of these 16 patients were free of
invasive ventilatory support. At the end of the study (with individual patient treatment durations
ranging from 60 to 150 weeks; mean follow-up period of 119 weeks) 14 of 16 patients were alive and

9 of 16 patients were alive and free of invasive ventilatory support. One additional patient died after
study end and another one after withdrawal from the study.
Comparison of survival curves from time of diagnosis versus the untreated historical cohort was made
using a Cox proportional hazards regression analysis. Patients treated with Myozyme demonstrated
prolonged survival as compared to survival in an untreated historical cohort (see Table 2).

Echocardiographic indices of cardiomyopathy improved as measured by a decrease in left ventricular
mass (LVM). After 52 weeks of treatment, LVM decreased from baseline in all 14 patients with
available data and was within normal limits in 3 of 14 patients. After the first year (64 up to
130 weeks) of treatment LVM further decreased in 8 patients. At 104 weeks of treatment LVM
assessments were available for 8 patients, of which 5 decreased to within normal limits.
As measured by motor performance age-equivalent scores of the Alberta Infant Motor Scale (AIMS),
seven of the 18 patients made motor development gains during the study and were walking
independently by the last study assessment (with individual patient treatment durations ranging from
52 to 130 weeks; mean follow-up period of 94 weeks). An additional 4 patients made motor
development gains during the study and were sitting independently by the last study assessment (with
individual patient treatment durations ranging from 78 to 130 weeks; mean follow-up period of
110 weeks), although they did not have functional use of the legs. The remaining 7 patients made no
clinically significant motor gains or were unable to sustain the motor gains made and had very limited
motor movement by the last study assessment (with individual patient treatment durations ranging
from 52 to 142 weeks; mean follow-up period of 103 weeks).
After 52 weeks of treatment 14 of 18 patients (77.8%) had maintained or improved weight-for-age
percentiles (above the 3rd percentile), 14 of 15 patients (93.3%) were above the 3rd percentile for
length and 12 of 15 patients (80.0%) were above the 3rd percentile for head circumference. In the
second year of treatment, 15 out of 17 patients had further improved weight-for-age percentiles (with
individual patient treatment durations ranging from 78 to 142 weeks; mean follow-up period of
111 weeks), 10 out of 16 patients had further improved length-for-age percentiles (with individual
patient treatment durations ranging from 90 to 130 weeks; mean follow-up period of 113 weeks) and
11 out of 15 patients had further improved head circumference-for-age percentiles (with individual
patient treatment durations ranging from 90 to 130 weeks; mean follow-up period of 110 weeks). At
104 weeks of treatment, all 13 patients with available data had maintained or improved weight-for-age
percentiles (above the 3rd percentile), all 12 patients with available data were above the 3rd percentile
for length and all 12 patients with available data were above the 3rd percentile for head
circumference.
Analyses of efficacy did not reveal meaningful differences between the 2 dose groups with respect to
survival, invasive ventilator-free survival, any ventilator-free survival, decrease in LVM, gains in
growth parameters and acquisition of motor milestones. Based on these results the 20 mg/kg qow dose
is recommended.
Infantile-onset Pompe disease; clinical trial in patients aged 6 months to 3.5 years

A second open-label clinical trial also assessed the safety and efficacy of Myozyme in 21 patients
with predominantly a non-typical form of infantile-onset Pompe disease who ranged in age from
6 months to 3.5 years at initiation of treatment. Patients received 20 mg/kg Myozyme once every two
weeks for 52 weeks except for 8 patients who received 40 mg/kg after at least 26 weeks of treatment.
After 52 weeks all patients continued treatment for a total duration of more than 3 years (168 weeks
with a median of 121 weeks).
The primary endpoint of the pivotal trial was the proportion of patients who were alive. After
52 weeks of treatment, 16 of 21 patients (76.2%) treated with Myozyme were alive. After 104 weeks
of treatment, 14 of 21 patients (66.7%) were alive and 1 patient was alive but had discontinued from
the study. These proportions were maintained up to the end of the study (with individual patient
treatment durations ranging from 1 to 168 weeks; mean follow-up period of 109 weeks). In the
untreated historical cohort 5 of 47 patients (10.6%) for whom data were available, were alive at age
30 months (2.5 years).
Survival in the treated patients was compared to survival in a similar historical cohort of untreated
subjects using a Cox proportional hazards regression analysis (See Table 3).
Table 3: Results for endpoint survival using the Cox regression model

Additional efficacy data showed that of 16 patients who were free of invasive-ventilator support at
baseline, 7 remained so after 104 weeks of treatment. The 9 remaining patients either died (5 patients)
or became invasive-ventilator dependent (4 patients). All 5 patients who were receiving invasive
ventilation at baseline continued to require ventilation throughout the study (4 patients survived
beyond week 104 and one patient died).
After 52 weeks of treatment, LVM decreased from baseline in all 12 patients with available data and
was within normal limits in 6 of 12 patients. After the first year (58 up to 168 weeks) of treatment
LVM further decreased in 9 out of 12 patients with available data. At 104 weeks of treatment LVM
assessments were available for 10 patients, of which 9 decreased to within normal limits.
After 52 weeks of treatment, 3 out of 8 patients with available data made gains in motor function over
baseline as measured by raw scores and age-equivalent scores from baseline in the AIMS. Six of the
11 patients with available data continued to make motor development gains beyond Week 52 (with
individual patient treatment durations ranging from 58 to 168 weeks; mean follow-up period of
121 weeks), including 3 patients ambulatory and 3 patients with only functional sitting skills by the
last study visit. The remaining 5 patients showed no significant change in motor development beyond
Week 52 (with individual patient treatment durations ranging from 104 to 168 weeks; mean follow-up
period of 140 weeks), including 4 patients with no significant motor skills in any of the positions
evaluated and 1 patient with only functional sitting skills by the last study visit.
The vast majority of patients with infantile-onset Pompe disease treated with Myozyme demonstrate
improvement in cardiac function as well as stabilisation or improvements in growth parameters.
However, motor and respiratory responses to treatment have been more variable. Patients with
infantile-onset Pompe disease who demonstrated motor gains, had greater preservation of motor
function and lower glycogen content in the quadriceps muscle at baseline. It is noteworthy that a
higher proportion of patients with better motor outcomes show stability or improvement in growth

parameters (weight), while the large majority of patients, regardless of their motor outcomes or
baseline features, show reversal of cardiomyopathy as measured by changes in LVM Z-score.
The totality of the data suggests that early diagnosis and treatment at an early stage of disease may be
critical to achieve the best outcomes in these infantile onset patients.
Late-onset Pompe disease; pivotal clinical trial
The safety and efficacy of Myozyme was assessed in a randomized, double-blind, placebo-controlled
study in 90 patients with late-onset Pompe disease who ranged in age from 10 to 70 years at initiation
of treatment and were all naive to enzyme replacement therapy. Patients were randomized in a 2:1
ratio and received 20 mg/kg Myozyme (n=60) or placebo (n=30) once every two weeks for 78 weeks
(18 months).
The co-primary efficacy outcome assessments were distance walked (meters) in 6 minutes (6-Minute
Walk Test, 6MWT) and FVC (Forced Vital Capacity) % predicted in the sitting position. After
78 weeks, patients treated with Myozyme showed improvement in distance walked as measured by
6MWT and stabilization of pulmonary function as measured by FVC % predicted as compared to
placebo-treated patients. The distance walked in 6 minutes increased by a median of 15.0 meters for
Myozyme-treated patients and decreased by a median of 7.5 meters for placebo-treated patients,
indicating a statistically significant Myozyme treatment effect compared to placebo (p=0.0283). The
% predicted FVC changed by a median of 0.0 for Myozyme-treated patients and decreased by a
median of 3% for placebo-treated patients, indicating a statistically significant treatment effect
(p=0.0026). The results are shown in Table 4.

Late-onset Pompe disease; other clinical trials and analyses
Three independent, open-label, single arm, investigator-initiated studies with Myozyme were
conducted:
• One study in Italy enrolled 74 late-onset patients with up to 48 months follow up.
• One study in Germany enrolled 38 late-onset patients with 36 months follow up.
• One study in the Netherlands enrolled 69 late-onset patients with a median follow-up of 23
months.

These three studies with Myozyme (with a follow up of at least 3 years in two studies and a median of
23 months in the other study) suggested stabilisation or improvement of motor function and
stabilisation of pulmonary function.
In the above described study in 69 late-onset patients in the Netherlands, Myozyme showed an
improvement in muscle strength. However, muscle function only improved in wheelchair independent
patients and in those with less pronounced muscle weakness.
In two additional open-label clinical trials with Myozyme with a follow-up of 24 months, ten patients
with severe late-onset Pompe disease (moderate to severe motor impairment and assisted ventilation)
showed a variable response on measures of motor and respiratory functions, mostly in the form of a
modest improvement (AGLU03105, AGLU04107).
An open-label clinical trial assessed the safety and efficacy of Myozyme in 5 patients with late-onset
Pompe disease who ranged in age from 5 to 15 years at initiation of treatment (AGLU02804). Patients
received 20 mg/kg Myozyme once every two weeks for 26 weeks. All patients were freely ambulatory
and all but one patient did not require any form of ventilator support (1 patient required nocturnal
non-invasive ventilation). Of the 3 patients with significant pulmonary involvement at
screening/baseline (percentage predicted forced vital capacity in the sitting position ranging from 58-
67%), two demonstrated clinically meaningful improvements in FVC (+11.5% and +16.0%) in the
sitting position by Week 26. Evaluation of motor function gave disparate results.
Ten patients with advanced late-onset Pompe disease (i.e. wheelchair-bound for 10/10 and ventilatordependent
for 9/10) aged 9-54 years were treated in expanded access programs with alglucosidase alfa
20-40 mg/kg once every two weeks for various periods of time between 6 months and 2.5 years. The
pulmonary benefits observed in patients included a clinically meaningful improvement in FVC of
35% in one patient, and significant reductions in the number of hours of ventilator support needed in
2 patients. Benefits of treatment on motor function including the regaining of lost motor skills were
observed in some patients. Only one patient became wheelchair-free. In this group of patients a
variable response has also been seen with respect to motor function.
Pompe Registry
Medical or healthcare professionals are encouraged to register patients who are diagnosed with Pompe
disease at www.PompeRegistry.com. Patient data will be anonymously collected in this Registry. The
objectives of the “Pompe Registry” are to enhance the understanding of Pompe disease and to monitor
patients and their response to enzyme replacement therapy over time, with the ultimate goal of
improving clinical outcomes for these patients.

Infantile-onset Pompe disease
In a pivotal trial including 18 patients, the pharmacokinetics of alglucosidase alfa were evaluated in
15 patients with infantile-onset Pompe disease (all less than 6 months of age at treatment-onset) who
received doses of 20 mg/kg or 40 mg/kg alglucosidase alfa as an approximate 4 to 6.5-hour infusion,
respectively.
Distribution and elimination
After the first and sixth infusion of Myozyme, mean maximum plasma concentrations (Cmax) ranged
from 178.2 to 263.7 μg/ml for the 20 mg/kg and 40 mg/kg dose groups respectively. The mean area
under the plasma concentration-time curve (AUC∞) ranged from 977.5 to 1,872.5 μg•h/ml for the
20 mg/kg and 40 mg/kg dose groups. Mean plasma clearance (CL) was 21.4 ml/h/kg and mean volume
of distribution at steady state (Vss) was 66.2 ml/kg for both dose groups with small between-subject
variability of 15% and 11%, respectively. Mean plasma elimination half-life (t1/2) was 2.75 hours for
the two dose groups.

Linearity/non linearity
Pharmacokinetics were dose proportional and did not change over time.
The pharmacokinetics of alglucosidase alfa were also evaluated in a separate trial in 21 patients with
infantile-onset Pompe disease (all aged between 6 months and 3.5 years at treatment-onset) who
received doses of 20 mg/kg of alglucosidase alfa. In 12 patients with available data the AUC∞ and
Cmax were approximately equivalent to those observed for the 20 mg/kg dose group in the pivotal trial.
The t½ of approximately 2-3 hours was also similar in this group of patients.
Late-onset Pompe disease
The pharmacokinetics of alglucosidase alfa were evaluated in a trial in 5 patients with late-onset
Pompe disease aged 6-15 years who received 20 mg/kg alglucosidase alfa once every two weeks.
There was no difference in the pharmacokinetic profile of alglucosidase alfa in these juvenile lateonset
patients compared to infantile-onset patients.
The pharmacokinetics of alglucosidase alfa were studied in a population analysis of 32 late-onset
Pompe disease patients from the randomized, double-blind, placebo-controlled study ranging in age
from 21 to 70 years who received Myozyme 20 mg/kg once every two weeks. AUC∞ and Cmax were
similar at week 0, 12 and 52 visits indicating alglucosidase alfa pharmacokinetics were not timedependent
(Table 5).
Distribution and elimination

There was no evidence that IgG antibodies to alglucosidase alfa affected pharmacokinetics. Higher
mean clearance, lower mean AUC∞, and lower mean Cmax were observed in 5 patients who tested
positive for inhibition of cellular uptake of enzyme. However, there was no apparent association
between inhibition of uptake and the co-primary efficacy endpoints (see section 4.4).

Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, single and repeated dose toxicity. No significant adverse findings on embryofoetal
development were observed in a mouse and a rabbit embryofoetal study and no significant adverse
findings were observed in a mouse fertility and early embryonic development study. In the rabbit
embryofoetal development study, following administration of Myozyme (10-40 mg/kg/day) with
coadministration of diphenhydramine, a treatment-related increase in the incidence of abortions and
early delivery was observed. This effect was partly attributable to maternal toxicity, as a significant
decrease in feed consumption and body weight gain was observed.

Mannitol (E421)
Sodium dihydrogen phosphate monohydrate (E339)

Disodium phosphate heptahydrate (E339)
Polysorbate 80 (E433)

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.

Store in a refrigerator (2°C - 8°C).
For storage conditions after dilution of the medicinal product, see section 6.3.

50 mg of powder in a vial (Type 1 glass) with a stopper (siliconised butyl) and a seal (aluminium)
with a flip-off cap (plastic). Pack sizes of 1, 10 or 25 vials.
Not all pack sizes may be marketed.

Myozyme has to be reconstituted with water for injections, then diluted with sodium chloride 9 mg/ml
(0.9%) solution for injection and then administered by intravenous infusion. Reconstitution and
dilution should be performed in accordance with good practice rules, particularly for the respect of
asepsis.
Due to the proteinaceous nature of the product, particle formation may occur in the reconstituted
solution and final infusion bags. Therefore, a 0.2 micron low protein binding in-line filter should be
used for administration. It was demonstrated that the use of a 0.2 micron in-line filter removes visible
particles and does not result in an apparent loss of protein or activity.
Determine the number of vials to be reconstituted based on the individual patient’s dose regimen
(mg/kg) and remove the required vials from the refrigerator in order to allow them to reach room
temperature (approximately 30 minutes). Each vial of Myozyme is for single use only.
Use aseptic technique
Reconstitution
Reconstitute each 50 mg vial of Myozyme with 10.3 ml water for injections. Add the water for
injections by slow drop-wise addition down the side of the vial and not directly onto the lyophilised
cake. Tilt and roll each vial gently. Do not invert, swirl or shake the vial. The reconstituted volume is
10.5 ml containing 5 mg/ml, and appears as a clear, colourless to pale yellow solution which may
contain particles in the form of thin white strands or translucent fibres. Perform an immediate
inspection of the reconstituted vials for particulate matter and discoloration. If upon immediate
inspection foreign particles other than those described above are observed, or if the solution is
discoloured, do not use. The pH of the reconstituted solution is approximately 6.2.

After reconstitution, it is recommended to promptly dilute the vials (see below).
Dilution
When reconstituted as above, the reconstituted solution in the vial contains 5 mg alglucosidase alfa
per ml. The reconstituted volume allows accurate withdrawal of 10.0 ml (equal to 50 mg) from each
vial. This should then be further diluted as follows: Slowly withdraw the reconstituted solution from
each vial until the volume for the patient’s dose is obtained. The recommended final concentration of
alglucosidase in the infusion bags ranges from 0.5 mg/ml to 4 mg/ml. Remove airspace within the
infusion bag. Also remove an equal volume of sodium chloride 9 mg/ml (0.9%) solution for injection,
that will be replaced with reconstituted Myozyme. Slowly inject the reconstituted Myozyme directly
into the sodium chloride 9 mg/ml (0.9%) solution for injection. Gently invert or massage the infusion
bag to mix the diluted solution. Do not shake or excessively agitate the infusion bag.
The final infusion solution should be administered as close to preparation time as possible.
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.