Extension Study of Protocol ENB-002-08 - Asfotase Alfa Treatment in Severely Affected Infants and Young Children With Hypophosphatasia (HPP)

• To determine the long-term tolerability of subcutaneous (SC) Asfotase Alfa [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  The time points will be pre-treatment (Baseline from the 002 study) to Month 60 of the 003 study which represents 66 months of treatment.
• To assess the long-term efficacy of Asfotase Alfa in treating rickets in infants and young children with HPP [ Time Frame: 60 Months ] [ Designated as safety issue: No ]
  The time points will be pre-treatment (Baseline from the 002 study) to Month 60 of the 003 study which represents 66 months of treatment.

• To assess the long-term pharmacodynamics (PD) of SC Asfotase Alfa [ Time Frame: 60 Months ] [ Designated as safety issue: No ]
  The time points will be pre-treatment (Baseline from the 002 study) to Month 60 of the 003 study which represents 66 months of treatment.
• To assess the effect of SC Asfotase Alfa on growth and development [ Time Frame: 60 Months ] [ Designated as safety issue: No ]
  The time points will be pre-treatment (Baseline from the 002 study) to Month 60 of the 003 study which represents 66 months of treatment.
• To assess the effect of SC Asfotase Alfa on mortality and other clinical signs and symptoms of HPP in infants and young children [ Time Frame: 60 Months ] [ Designated as safety issue: No ]
  The time points will be pre-treatment (Baseline from the 002 study) to Month 60 of the 003 study which represents 66 months of treatment.

This clinical trial is being conducted to study long-term tolerability and efficacy outcomes in severely infected infants and young children with hypophosphatasia (HPP) being treated with an investigational study drug called Asfotase Alfa.

Asfotase Alfa was formerly referred to as ENB-0040

This is an open-label extension study of Asfotase Alfa in as many as 10 severely affected infants and young children with HPP who previously received Asfotase Alfa treatment in Enobia-sponsored clinical trial ENB-002-08. Infants and young children who have HPP and who completed study ENB-002-08 in a compliant manner (in the opinion of the Sponsor and Investigator) may continue Asfotase Alfa treatment under protocol ENB-003-08 if eligibility criteria are met and informed consent is received from the parent or other legal guardian. The Asfotase Alfa dose regimen will continue as established during previous study participation, with provisions for adjustment based on patient's weight. Additional dose adjustments may also be considered for lack of efficacy or safety-related concerns after review and discussion with the Enobia Medical Monitor. Patients will receive SC Asfotase Alfa for 60 months. Baseline assessments may coincide with the final visit of the previous study, and subsequent assessments will be scheduled every 3 months during the first 12 months of the study and every 6 months thereafter.

Inclusion Criteria

• Compliant and satisfactory completion, in the opinion of the Sponsor and Investigator, of study ENB 002 08
• Written informed consent by parent or other legal guardian prior to any study procedures being performed
• Parent or other legal guardian willing to comply with study requirements

Exclusion Criteria

• History of sensitivity to any of the constituents of the study drug
• Clinically significant disease that precludes study participation, in the Investigator's opinion
• Enrollment in any study involving an investigational drug, device, or treatment for HPP(e.g., bone marrow transplantation)