Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total)

Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total)

Control (no asfotase alfa) during primary treatment period (first 24 weeks)

Subjects from Cohort 1 and Cohort 2 treated with asfotase alfa during primary treatment period (first 24 weeks)

PPi Change from Baseline to Week 24

Two-sided with p-value threshold <0.05 for statistical significance

Estimate and exact confidence interval are from Hodges-Lehmann-Sen method for location shift in distribution between the treatment group and the control group.

If p-values were less than 0.05 and the Hodges-Lehman-Sen estimate favored asfotase alfa (eg, it had a negative sign indicating the between-group differences in change from Baseline favored treated patients), then superiority over control was claimed.

Primary Treatment Period (first 24 week). Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total).

Primary Treatment Period (first 24 weeks). Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total).

No asfotase alfa during primary treatment period: (first 24 weeks).

All subjects from Cohort 1, Cohort 2, or Control group with any asfotase alfa exposure. During primary treatment period, N=13. During open-label extension treatment period, N=19.

Asfotase alfa: Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (total of 2.1 mg/kg/week) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa: Cohort 2: Daily SC injections of 0.5 mg/kg Asfotase Alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

All subjects from Cohort 1, Cohort 2, or Control group with any asfotase alfa exposure. During primary treatment period, N=13. During open-label extension treatment period, N=19.

Hip Total BMC Change from Baseline to Week 24

Two-sided with p-value threshold <0.05 for statistical significance

Asfotase alfa: Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (total of 2.1 mg/kg/week) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa: Cohort 2: Daily SC injections of 0.5 mg/kg Asfotase Alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

All subjects from Cohort 1, Cohort 2, or Control group with any asfotase alfa exposure. During primary treatment period, N=13. During open-label extension treatment period, N=19.

Hip Total Change from Baseline to Week 24

Two-sided with p-value threshold <0.05 for statistical significance

Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Subjects From Cohort 1 and Cohort 2 treated with asfotase alfa (N=13) during Primary Treatment Period, and all subjects exposed to asfotase alfa (N=19) during extension treatment period.

Week 24 Change from Baseline

Two-sided with p-value threshold <0.05 for statistical significance

Estimate and exact confidence interval are from Hodges-Lehmann-Sen method for location shift in distribution between the treatment group and the control group

Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Subjects from primary treatment period asfotase alfa groups.

Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Subjects from primary treatment period asfotase alfa groups.

Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Subjects from primary treatment period asfotase alfa groups.