Pharmacokinetics, Pharmacodynamics And Safety Study Of Elelyso(tm) In Pediatric Subjects With Type 1 Gaucher Disease

This study (B3031003) is an open-label study in pediatric subjects with Type 1 Gaucher
Disease to characterize PK, PD and safety following an infusion of taliglucerase alfa in at
least 5 subjects with body weight less than 15 kg; at least 5 subjects with body weight 15 to
less than 20 kg; and at least 5 subjects with body weight of 20-25 kg. The PK sample
collection will take approximately 4 hours to complete and will be performed one month or up
to 6 months after the subject's first taliglucerase infusion in the registry study. The
subject will be contacted the day after the PK samples are collected to assess any continuing
or new adverse events and to review the subject's concomitant medications. Body weight at the
time of the PK blood draw will determine the weight category for each subject. Subjects
enrolled into the study will be assigned the same unique subject number assigned to them in
the registry study (B3031002). This will allow linkage to relevant data from the registry
study for analysis in this study.

For the purposes of this study, baseline evaluations will be obtained from the registry study
and must be performed prior to the subject's first dose of taliglucerase alfa. The Month 6
and Month 12 evaluations will be performed 6 months and 12 months after the start of
taliglucerase alfa treatment, respectively.

Subjects will be eligible for the PK study (B3031003) only if the PD assessments (spleen
volume/size, hemoglobin/platelet counts and height/weight measurements) immunogenicity data
and Gaucher disease diagnostic history are available from the registry study baseline visit
and prior to the start of taliglucerase alfa treatment. If liver volume/size is available, it
will also be analyzed but is not necessary for eligibility for the PK study.

Pediatric subjects prescribed 60 units/kg of taliglucerase alfa every other week by their
physician will be recruited from the registry study. Subjects can be screened for the PK
study at the same time as they are enrolled into the registry study (ERT treatment-naïve
subjects) or up to 6 months after they are enrolled into the registry study (previously ERT
naïve subjects) if PD assessments (spleen volume/size, hemoglobin/platelet counts and
height/weight measurements), immunogenicity data and Gaucher disease diagnostic history
(residual enzyme activity and genotype data) were performed at baseline of the registry study
and prior to the start of taliglucerase alfa treatment.

Baseline data from the registry study for PD and immunogenicity testing are defined as PD
measurements (spleen volume/size, liver volume/size (if available), hemoglobin and platelet
counts and growth measures), Gaucher disease diagnostic history and immunogenicity samples
that were collected at entry into the registry study and prior to the start of taliglucerase
alfa treatment.

For the secondary PD endpoints, spleen volume/size and liver volume/size (if available) will
be measured using MRI, CT or ultrasound, whichever is the standard of care according to the
investigator. The method used to measure spleen and liver volume/size at Baseline will be the
same one used at Month 12. Change from Baseline and percent change from Baseline at Month 12
of registry study will be calculated for spleen volume, liver volume (if available),
hemoglobin and platelet counts, and growth measures (height, weight and Z-scores).

For each subject enrolled in this study, safety data while on taliglucerase alfa, starting
from the baseline visit (entry into the registry study) and continuing until 28 days after
the Month 12 PD data collection visit, will be obtained for reporting.

Safety assessments for the study will include collection of all adverse event and serious
adverse event data, including serious hypersensitivity reactions, procedures for
immunogenicity testing (ie, detection and titers of binding and neutralizing antibodies and
detection of IgE antibodies) as well as vital signs taken as standard of care during
infusions. A pre-dose blood sample for testing of antidrug antibodies (ADA) on the day of PK
Sample Visit will be collected in an effort to assess the impact of immunogenicity on PK.

Inclusion Criteria:

1. Male or female pediatric subjects with a diagnosis of Type 1 Gaucher disease (evidence
of leukocyte acid-glucosidase activity 30% of the mean of the reference range for
healthy persons), and meeting one of three weight categories: less than15 kg; 15 to
less than 20 kg or 20-25 kg.

2. ERT treatment-naïve, or able to perform the PK assessment within the initial 6 months
of initial Elelyso treatment (provided the subject was ERT naïve prior to the start of
Elelyso).

3. Have had baseline (ie, prior to the first dose of study medication) PD measurements
(spleen volume/size measured by MRI, CT or ultrasound, hemoglobin/platelet counts and
growth measures including height and weight), immunogenicity sample collection and
Gaucher disease diagnosis history documented in advance of treatment start.

4. Presence of splenomegaly at baseline defined as spleen volume/size measurement of 5
MN.

5. Subjects prescribed the nominal dose of 60 units/kg every two weeks and can tolerate
an infusion rate of 1 mL/min.

6. Evidence of a personally signed and dated informed consent document from parent/legal
guardian (or adult caregiver) capable of providing informed consent indicating that
the subject's parent(s)/legal guardian has been informed of all pertinent aspects of
the study before any screening procedures are performed. When age appropriate, written
assent must also be obtained.

7. Have parent/legal guardian (or adult caregiver) capable and willing to comply with
scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

1. Evidence or history of clinically significant issue or the presence of a medical,
emotional, behavioral or psychological condition that, in the judgment of the
Investigator, would interfere with the subject's participation in the study, cause
harm to the subject or decrease compliance with the study requirements.

2. Treatment with an investigational drug within 30 days (or as determined by the local
requirement) or 5 half-lives preceding the PK sample collection visit, whichever is
longer.

3. A diagnosis of Type 2 or 3 Gaucher disease, or the presence of neurological signs and
symptoms characteristic of Type 2 or 3 Gaucher disease.

4. Any change during the registry study to the subjects dose of taliglucerase alfa
infusion (ie, change from 60 units/kg every two weeks to a different dose of
taliglucerase alfa) or a change in infusion duration or rate or a change of ERT
medication (ie, switch from taliglucerase alfa to a different ERT).

5. In the judgment of the Investigator, the subject's vital signs (eg, blood pressure,
pulse) prior to infusion on the day of the PK visit indicate that participation in the
study would not be in the study candidate's best interest.

6. A hemoglobin level of <10 g/dL within 30 days of the PK sample visit or on the day of
the PK sample visit.

7. History of sensitivity to heparin or heparin-induced thrombocytopenia. (Note: applies
only if heparin lock or flush is to be used on the day of the PK sample visit).

8. Parents or legal guardians who are investigational site staff members directly
involved in the conduct of the study and their family members, children of site staff
members otherwise supervised by the Investigator, or subjects who are children of
Pfizer employees directly involved in the conduct of the study.