Safety and Efficacy of Asfotase Alfa in Juvenile Patients With Hypophosphatasia (HPP)

Asfotase Alfa was formerly referred to as ENB-0040

Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease
characterized by defective bone mineralization and impaired phosphate and calcium regulation
that can lead to progressive damage to multiple vital organs, including destruction and
deformity of bones, profound muscle weakness, seizures, impaired renal function, and
respiratory failure. There are no approved disease-modifying treatments for patients with
this disease. There is also limited data available on the natural course of this disease over
time, particularly in patients with the juvenile-onset form.

Efficacy analyses were prospectively defined in the protocol with a comparison to historical
controls. The historical control group came from patients whose characteristics matched as
closely as possible the entry criteria for the trial. The control group included all patients
who had x-rays within the age range defined by the inclusion criteria of this study (5 to 12
years of age, inclusive, with open growth plates).

The pre-specified plan for analysis was to combine the two asfotase alfa treated groups
(asfotase alfa 2 mg/kg subcutaneous (SC) injection three times per week or 3 mg/kg
subcutaneous (SC) injection three times per week) and compare them to historical controls.

Inclusion Criteria:

1. Written informed consent from parent or legal guardian prior to participation

2. Patients > 5 and < 12 years of age with open growth plates at time of enrollment

3. Tanner stage of 2 or less indicating pre-pubescence

4. Documented history of HPP, as evidenced by:

- Presence of HPP-related rickets on skeletal radiographs of the wrist and knee

- Serum alkaline phosphatase (ALP) below age-adjusted normal range

- Plasma PLP at least twice the upper limit of normal

5. 25(OH) vitamin D level > 20 ng/mL

6. Ability of patient and parent/guardian to comply with study requirements

Exclusion Criteria:

1. Serum calcium or phosphorus below age-adjusted normal range

2. History of sensitivity to any study drug constituent

3. Medical condition, serious intercurrent illness, or other extenuating circumstance
that, in the opinion of the Investigator, may significantly interfere with study
compliance, including all prescribed evaluations and follow-up activities

4. Treatment with an investigational drug within 1 month before start of study drug

5. Current enrollment in any other study involving an investigational new drug, device,
or treatment for HPP (e.g., bone marrow transplantation)

6. Current evidence of a treatable form of rickets

7. Prior treatment with bisphosphonates

8. Bone fracture or orthopedic surgery within the past 12 months that, in the opinion of
the Investigator would interfere with the ability of study patient to comply with
study protocol

9. Major congenital abnormality other than those associated with HPP