Introduction

Asfotase alfa (trade name: Strensiq) has been approved in Germany since August 2015 for the treatment of childhood- or juvenile-onset hypophosphatasia (HPP). It is intended for long-term use.

Hypophosphatasia is a very rare inherited metabolic bone disease. It is caused by a defect in the gene that the body needs in order to make the enzyme known as alkaline phosphatase. If not enough alkaline phosphatase is produced, the bones can’t build up enough minerals such as phosphorous or calcium and they become less stable. This often results in skeletal deformation and joint inflammations.

There are different types of hypophosphatasia. The main ones include:

  • Perinatal or infantile hypophosphatasia: Signs of the disease first occur before six months of age.
  • Juvenile hypophosphatasia: Signs of the disease first occur between six months and 18 years of age.
  • The symptoms are more severe if the disease develops at an earlier age.

Asfotase alfa is a protein. The aim of treatment with this protein is to replace the missing enzyme and promote bone mineralization and stability.

Application

Asfotase alfa is injected under the skin. The dose is 2 mg per kilogram of body weight if 3 injections are given per week, and 1 mg per kilogram of body weight if 6 injections are given per week.

The drug is available in two different doses: One milliliter of the infusion solution contains either 40 mg or 100 mg of asfotase alfa.

Other treatments

Best supportive care (BSC) is the standard treatment for hypophosphatasia. Supportive care should be tailored to the patient’s individual needs. It aims to relieve symptoms such as pain and improve quality of life.

Assessment

In 2019 the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of asfotase alfa when compared with the standard treatments for hypophosphatasia.

The manufacturer provided three studies on perinatal or infantile hypophosphatasia: Two studies involving a total of 80 children looked into treatment with asfotase alfa in children aged 5 years and under. For purposes of comparison, one other study analyzed the medical records of 48 children who had been given BSC (without asfotase alfa) over their first 5 years of life.

IQWiG’s analysis shows that the children whose medical records were analyzed weren't completely comparable to the children from the other two studies: For instance, there were differences in the age at which the disease developed and in how long the children were observed. So it’s only possible to draw tentative conclusions about the pros and cons of asfotase alfa.

What are the advantages of asfotase alfa?

Overall survival: Based on these estimates, asfotase alfa reduces the number of deaths in children aged 5 years and under who have perinatal or infantile hypophosphatasia. It's not clear how much of a difference it makes.

What remains unanswered?

Based on the studies, it wasn’t possible to say how treatment with asfotase alfa affected the symptoms of the disease, such as breathing problems or health-related quality of life. It was not possible to assess the side effects, either. But the studies don’t suggest that there would be any severe side effects that would outweigh the advantages of the treatment.

It’s also unclear which pros or cons asfotase alfa would have compared to the standard treatment in patients aged 5 years and up who have perinatal or infantile hypophosphatasia or in patients who have juvenile hypophosphatasia. The manufacturer didn’t provide any suitable data with which to look into this.

More information

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the review and the hearings received, the G-BA passed a resolution on the added benefit of asfotase alfa (Strensiq).