Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults 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 limited data available on the natural course of this disease
over time, particularly in patients with the juvenile-onset form.

Inclusion criteria:

Patients must meet all of the following inclusion criteria to be eligible for participation
in this study:

- Patients or their legal representative(s) must provide written informed consent prior
to undergoing any study-related procedures

- Patients must be ≥ 13 and ≤ 65 years of age at the time of study enrollment

- Female patients of childbearing potential and sexually mature males must agree to use
a medically acceptable form of birth control; for the purposes of this study, females
are considered of non-childbearing potential if they are surgically sterile (i.e.,
have undergone a total hysterectomy, bilateral salpingo-oophorectomy or tubal
ligation) or are post-menopausal, defined as having complete cessation of menstruation
for at least 1 year after 45 years of age

- Patients must have a pre-established clinical diagnosis of HPP as indicated by:

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

- Plasma PLP at least twice the upper limit of normal (no vitamin B6 administered
for at least 1 week prior to determination)

- Evidence of osteopenia or osteomalacia on skeletal radiographs

- Patients must have osteomalacia on bone biopsy, characterized by an MLT z-score of +2
or more (results from ENB-001-08 may be used)

- Patients must be willing to comply with study procedures and the visit schedule

Exclusion criteria:

Patients will be excluded from participation in this study if they meet any of the
following exclusion criteria:

- Women who are pregnant or lactating

- History of sensitivity to tetracycline

- Serum calcium or phosphate levels below the normal range

- Serum 25(OH) vitamin D below 20 ng/mL

- Serum creatinine or parathyroid hormone (PTH) levels above the upper limit of normal

- 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

- Orthopedic surgery within 12 months prior to study entry that may interfere with the
ability to perform functional assessments for the study

- Prior treatment with bisphosphonates within 2 years of study entry for any length of
time or for more than 2 years at any time point; for patients with prior
bisphosphonate use that is allowed, the bone resorption markers serum C-telopeptide
and urine N-telopeptide or urine deoxypyridinoline must also be within the normal
range or elevated to be eligible for study participation

- Treatment with PTH within 6 months prior to the start of asfotase alfa administration

- Participation in an interventional or investigational drug study within 30 days prior
to study participation