Asfotase Alfa May Significantly Benefit Children with Hypophosphatasia

Doctor speaks with girl and her mother
Doctor speaks with girl and her mother
Treatment over 5 years appears to be safe and effective.

SEATTLE – Asfotase alfa appears to be well tolerated over 5 years of treatment and leads to normalization of skeletal manifestations and improved functional ability in children with hypophosphatasia, according to new data.

The study was presented at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting.

Researchers tracked a group of children with hypophosphatasia for over 5 years and found that treatment with asfotase alfa substantially improved the skeletal radiographic manifestations of hypophosphatasia. The children also experienced highly significant improvements in the standardized tests of their functional ability, including the 6-minute walk test.

“The results of the standardized tests were supported by the parent-reported outcomes of highly significant improvements in their activities of daily living, including dressing, walking, eating, gripping, stamina, ability to participate in sports, and especially improvement in pain, comfort, and overall happiness. In addition, there were important increases in the height and weight of the children during this study time interval,” said lead study author Cheryl Rockman-Greenberg, MD, who is a distinguished professor in the department of pediatrics and child health at the University of Manitoba and a clinician scientist at the Children’s Hospital Research Institute of Manitoba in Canada.

At the meeting, Dr Rockman-Greenberg presented new results from the extension phase of a multinational, open-label, phase 2 study of asfotase alfa, administered subcutaneously at 6 mg/kg per week, in children with hypophosphatasia (aged 5-12 years at study entry).

Twelve of 13 patients completed the original 6-month study, entered the extension study, and received at least 5 years of treatment with asfotase alfa.

Results showed that median 6-minute walk distance improved from 61% of that predicted for healthy peers at baseline to 85% at 6 months and 83% at 5 years of treatment with asfotase alfa, indicating sustained improvements in walking over 5 years. 

The researchers measured strength and agility as a composite of Running Speed/Agility and Strength sub-tests of Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2). 

They found that strength and agility improved from below normal at baseline to within the normal range at 1 year of treatment, which was sustained through 5 years.

Dr Rockman-Greenberg said that asfotase alfa appears to be very effective in treating the serious bone manifestations of hypophosphatasia and improving quality of life. She also noted the safety profile to date is very encouraging. 

“The main side effect being skin reactions at the injection sites including redness, purplish discoloration, and changes in the texture of the skin, but none were considered serious enough to withdraw from the study. There were no serious adverse events reported in this study group,” Dr Rockman-Greenberg told Endocrinology Advisor.

In patients treated with asfotase alfa, there was a significant and clinically meaningful reduction in disability, with scores decreasing from a median of 1.0 at baseline to 0.25 at 6 months to 0.0 at 2 years on the Child Health Assessment Questionnaire (CHAQ) Disability Index. This improvement was sustained through 5 years of treatment.

Asfotase alfa is approved in Japan as a treatment for patients with hypophosphatasia and in the European Union and in Canada as a treatment for patients with pediatric-onset hypophosphatasia. The U.S. Food and Drug Administration (FDA) has granted it Breakthrough Therapy designation. 

“[Hypophosphatasia] has to date been an untreatable disease; thus, the option of an effective treatment is tremendously important. It is also a condition where measurement of only a single blood parameter, serum alkaline phosphatase, corrected for age and gender of the patient, can give you the best clue to the underlying diagnosis,” said Dr Rockman-Greenberg. 

“Careful history and physical examination and timely measurement of serum alkaline phosphatase are all you need to make a diagnosis of [hypophosphatasia], a disorder for which previously there was no effective treatment. But that appears to have changed with the promise of asfotase alfa.”

However, she said ongoing surveillance and careful follow-up of patients with hypophosphatasia are needed. These are key to ensuring efficacy and safety of the drug. 

In a separate analysis presented at this meeting, clinically significant improvements in functional mobility compared with historical controls were observed in patients with juvenile-onset hypophosphatasia who were treated with asfotase alfa in an ongoing, open-label phase 2 study.

Katherine Madson, MD, PhD, with the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospitals for Children in St. Louis, Missouri, presented results from a functional mobility analysis that assessed gait, or walking ability, in patients aged 5 to 15 years with juvenile-onset hypophosphatasia. The analysis included 8 patients treated with asfotase alfa. The researchers observed improved functional mobility, as reflected by significant improvements in key measures of walking ability.


  1. Rockman-Greenberg C. Abstract 1071: Asfotase alfa: Sustained Efficacy and Tolerability in Children with Hypophosphatasia Treated for 5 Years. 
  2. Madson K. Abstract MO0059: Improved Functional Mobility with Asfotase alfa Treatment in Childhood Hypophosphatasia. Both presented at: American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting; Oct. 9-12, 2015; Seattle.