Strensiq (asfotase alfa)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved October 2015

Specific Treatments:

hypophosphatasia

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General Information

Strensiq (asfotase alfa) is a tissue nonspecific alkaline phosphatase. 

Strensiq is specifically indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia.

Strensiq is supplied as an injection for subcutaneous administration. The recommended dosing is as follows:

Perinatal/Infantile-Onset HPP

Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen. The dose may be increased to 3 mg/kg three times per week for insufficient efficacy.

Juvenile-Onset HPP

Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen.

Preparation and Weight-Based Dosing

Caution: Do not use the 80 mg/0.8 mL vial in pediatric patients weighing less than 40 kg because the systemic asfotase alfa exposure achieved with the 80 mg/0.8 mL vial (higher concentration) is lower than that achieved with the other strength vials (lower concentration). A lower exposure may not be adequate for this subgroup of patients. • See full prescribing information for tables of weight-based dosing by treatment regimen.

 

Clinical Results

FDA Approval

 

The FDA approval of Strensiq was based on four prospective, open-label studies in 99 patients with perinatal, infantile- or juvenile-onset HPP who received treatment for up to 6.5 years during  Study results showed that patients with perinatal- and infantile-onset HPP treated with Strensiq had improved overall survival and survival without the need for a ventilator (ventilator-free survival). Ninety-seven percent of treated patients were alive at one year of age compared to 42 percent of control patients selected from a natural history study group. Similarly, the ventilator-free survival rate at one year of age was 85 percent for treated patients compared to less than 50 percent for the natural history control patients. Patients with juvenile-onset HPP treated with Strensiq showed improvements in growth and bone health compared to control patients selected from a natural history database. All treated patients had improvement in low weight or short stature or maintained normal height and weight. In comparison, approximately 20 percent of control patients had growth delays over time, with shifts in height or weight from the normal range for children their age to heights and weights well below normal for age. Juvenile-onset patients also showed improvements in bone mineralization, as measured on a scale that evaluates the severity of rickets and other HPP-related skeletal abnormalities based on x-ray images. All treated patients demonstrated substantial healing of rickets on x-rays while some natural history control patients showed increasing signs of rickets over time.

 

Side Effects

Adverse effects associated with the use of Strensiq may include, but are not limited to, the following: 

  • injection site reactions
  • lipodystrophy
  • ectopic calcifications
  • hypersensitivity reactions

Mechanism of Action

Hypophosphatasia is caused by a deficiency in the tissue non-specific alkaline phosphatase (TNSALP) enzyme, which leads to elevations in several TNSALP substrates, including inorganic pyrophosphate (PPi). Elevated extracellular levels of PPi block hydroxyapatite crystal growth which inhibits bone mineralization and causes an accumulation of unmineralized bone matrix which manifests as rickets and bone deformation in infants and children and as osteomalacia (softening of bones) once growth plates close, along with muscle weakness. Replacement of the TNSALP enzyme upon Strensiq treatment reduces the enzyme substrate levels.

Additional Information

For additional information regarding Strensiq or hypophosphatasia, please visit http://strensiq.com/