Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication STRENSIQ ® is indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP). STRENSIQ is a tissue nonspecific alkaline phosphatase indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP). ( 1 ) FDA label
Also known as Strensiq, ENB-0040, sALP-Fc-D10, Asfotase Alfa was formerly referred to as ENB-0040
asfotase alfa · 8 trials · 2 indications
Plasma PPi concentrations were determined using a specific enzyme-catalyzed reaction with a radiolabelled marker in a 3-step process. Baseline plasma PPi values were calculated by averaging pre-dose values from samples collected during the Run-in Period at -168, -156, -24, -12, and 0 hours before Baseline. Week 9 plasma PPi values were calculated using blood samples collected before administration of the 3rd dose. The analysis was a restricted maximum likelihood (REML)-based repeated measures mixed model with treatment, visit, sex, Baseline PPi, Baseline weight group (≥ median versus \< median), and study drug lot assignment as factors, and an unstructured covariance structure for within-participant correlation. Per inclusion criteria, participants had to have had a Screening PPi concentration of ≥3.9 micromolar (μM). Three participants (1 in each group) had Screening PPi concentrations of ≥3.9 μM, but Baseline PPi values ranged between 3.5 to 3.8 μM.
The effect of asfotase alfa treatment on skeletal manifestations of HPP (i.e., change in rickets severity) was measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale. Skeletal radiographs obtained at Week 24 were compared with skeletal radiographs obtained before initiation of treatment. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP-associated rickets) to +3 (indicative of complete or near complete healing of HPP-associated rickets).
Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa for all treated patients was assessed by the number of patients with 1 or more treatment-emergent adverse event.
Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma pyridoxal-5' phosphate (PLP)
Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi)
The safety and tolerability of daily subcutaneous (SC) injections of asfotase alfa was assessed by routine monitoring of patients for treatment-emergent adverse events (TEAEs) and injection-associated reactions (IARs).
Evaluation of radiographic change in rickets severity (as assessed by skeletal radiographs of the hands/wrists and knees) from the Baseline of Study ENB-006-09 (NCT00952484) to the End of Study (EOS) visit in Study ENB-008-10 using an ordinal RGI-C scale score. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP associated rickets) to +3 (indicative of complete or near complete healing of HPP associated rickets). The time points will be pre-treatment (Baseline from Study ENB-006-09) to the last radiographic assessment in Study ENB-008-10, which represents at least 72 months of treatment.
A 7-point RGI-C (radiographic global impression of change) score was used to rate change in rickets severity. Only those patients with a minimum score of +2 indicating substantial healing of rickets) were considered responders. Three pediatric radiologists not affiliated with the conduct of the study performed the ratings.
Outcome measure is the number of patients with 1 or more treatment-emergent adverse event. The time period is from Baseline in the ENB-003-08 study to the end of the ENB-003-08 study.
Outcome measure is the evaluation of radiographic change in rickets severity using a qualitative Radiographic Global Impression of Change (RGI-C) Scale. Skeletal radiographs obtained at the patient's last assessment were compared with skeletal radiographs obtained before initiation of treatment (Baseline in Study ENB-002-08 \[NCT00744042\]). The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP-associated rickets) to +3 (indicative of complete or near complete healing of HPP-associated rickets). The time period is pre-dose (Baseline from ENB-002-08 study) to the last assessment for each patient in the ENB-003-08 study, which represents up to 90 months of exposure for the combined studies.
A 7-point RGI-C (Radiographic Global Impression of Change) score was used to rate change in rickets severity. Scores ranged from -3 (severe worsening of rickets) to +3 (complete healing of rickets). Only those patients with a minimum score of +2 indicating substantial healing of rickets) were considered "responders". Three pediatric radiologists not affiliated with the conduct of the study performed the ratings. Average scores were derived for each patient at each assessment.
| Arm | Type | Description |
|---|---|---|
| Asfotase Alfa 0.5 mg/kg Dose | EXPERIMENTAL | Participants received 0.5 milligrams (mg) per kilogram (kg) of asfotase alfa administered subcutaneously (SC) 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1. |
| Asfotase Alfa 2.0 mg/kg Dose | EXPERIMENTAL | Participants received 2.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1. |
| Asfotase Alfa 3.0 mg/kg Dose | EXPERIMENTAL | Participants received 3.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1. |
| Asfotase alfa | EXPERIMENTAL | A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week) |
| Cohort 1 | EXPERIMENTAL | Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total) |
| Cohort 2 | EXPERIMENTAL | Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) |
| Concurrent Control | NO_INTERVENTION | Following completion of the Week 24 visit, all patients (including those randomized to the concurrent control cohort) may be eligible to participate in an open-label extension treatment period. In this extension period, all patients will be 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 will receive 1 mg/kg/day 6 days/week for an additional 48 weeks or until regulatory approval of the drug. |
| 2 mg/kg | ACTIVE_COMPARATOR | 2 mg/kg subcutaneous injection three times per week. |
| 3 mg/kg | ACTIVE_COMPARATOR | 3 mg/kg subcutaneous injection three times per week. |
| Name | Type | Description |
|---|---|---|
| Asfotase alfa | DRUG | - |
Inclusion Criteria: 1. Participants or their legal representative(s) provided written informed consent prior to undergoing any study-related procedures. 2. Participants were ≥18 years of age at Screening. 3. Participant had pediatric-onset hypophosphatasia (HPP), defined as onset of first sign(s)/s...
Asfotase alfa is an investigational therapy being studied for hypophosphatasia (HPP), a rare inherited disorder affecting bone and tooth mineralization. Clinical trials have enrolled patients with pediatric-onset HPP, including infants, children, and adults. It is not yet approved and remains in clinical development.
Asfotase alfa targets the ALPL gene product, tissue-nonspecific alkaline phosphatase (TNSALP), which is deficient in hypophosphatasia. By targeting this enzyme, the drug aims to restore alkaline phosphatase activity and improve bone mineralization in patients with HPP.
Asfotase alfa is being developed by AstraZeneca PLC, which trades on the Nasdaq under the ticker AZN. The company is responsible for the clinical development program in hypophosphatasia.
Asfotase alfa is in Phase 2 clinical development for hypophosphatasia. All eight of its registered trials are completed, and no active trials are currently listed. It is an investigational drug and has not been approved by the FDA.
Asfotase alfa has been studied in eight completed Phase 2 trials, including NCT02797821 in adults with pediatric-onset HPP, NCT01176266 in infants and children up to 5 years, and extension studies NCT01205152 and NCT01203826. These trials enrolled a total of 167 participants across multiple countries.