Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jul 25.
doi: 10.1007/s12325-025-03309-1. Online ahead of print.

Key Learnings from Clinical Research and Real-World Evidence on Asfotase Alfa Effectiveness in Hypophosphatasia: 10 Years Post-Approval

Aliya A Khan  1 , Eric T Rush  2   3 , Craig Wakeford  4 , Daniel Staub  5 , Maria Luisa Brandi  6
Affiliations
Review

Key Learnings from Clinical Research and Real-World Evidence on Asfotase Alfa Effectiveness in Hypophosphatasia: 10 Years Post-Approval

Aliya A Khan et al. Adv Ther. .

Abstract

First reported in 1948, hypophosphatasia (HPP) is a rare systemic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (ALP) enzyme. Patients with HPP experience skeletal and dental manifestations such as rickets/osteomalacia, fractures, pseudofractures, and premature tooth loss, as well as nonskeletal symptoms such as pain and muscle weakness, which result in impaired mobility and poor quality of life. For decades, no specific treatment was available for HPP and the disease was often fatal in infants. Asfotase alfa is a tissue-nonspecific ALP enzyme replacement therapy (ERT) that received first regulatory approval in 2015 in Japan, the European Union, and the United States for the treatment of HPP. This review draws from clinical trial findings, real-world evidence, and relevant case study data demonstrating the safety and effectiveness of asfotase alfa in improving a broad range of skeletal and nonskeletal manifestations in both pediatric and adult patients. Asfotase alfa has been shown to be well tolerated, with manageable side effects. Further, asfotase alfa treatment has improved survival and respiratory outcomes, skeletal outcomes, physical and motor function, pain, disability, and quality of life in patients with HPP. This evidence-based review aims to generate a foundation for improving the understanding of disease pathophysiology, hence enhancing the effectiveness of ERT in patients with HPP.

Keywords: Asfotase alfa; Bone; Effectiveness; Hypophosphatasia; Quality of life; Treatment.

Plain language summary

We conducted this research to understand the efficacy in clinical trials, effectiveness in real-world studies, and overall safety of asfotase alfa. Asfotase alfa is a treatment for hypophosphatasia, a rare disease identified in 1948. This review marks 10 years since asfotase alfa’s first approval in 2015. Hypophosphatasia leads to a variety of health issues, including bone problems like rickets and fractures, premature tooth loss, and muscle weakness, pain, and poor quality of life. Before asfotase alfa, there was no specific treatment, and the disease could be deadly in infants. We gathered and analyzed data from clinical trials, real-world patient experiences, and case studies. This comprehensive review focused on various outcomes in both children and adults with hypophosphatasia. We looked at survival rates, the need for respiratory support, improvements in bone and dental health, physical abilities, pain, disability, and overall quality of life. We also reviewed the safety of asfotase alfa. The findings from the past decade show that asfotase alfa is effective in managing the wide range of symptoms associated with hypophosphatasia, from bone-related issues to muscle weakness. It has significantly improved survival in infants showing symptoms before six months of age. Asfotase alfa has also enhanced patients’ quality of life. These results provide a solid base for healthcare providers to assess and treat hypophosphatasia and guide future research directions to further benefit patients.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of Interest: Aliya A. Khan has received honoraria from Amgen and Alexion and support from Ascendis, Calcilytix, Amolyt, and Alexion, AstraZeneca Rare Disease. Eric T. Rush has received consulting fees, support for attending meetings, and honoraria from Alexion, AstraZeneca Rare Disease. He is also on the Alexion advisory board and his institution has received grants from Alexion, AstraZeneca Rare Disease. Craig Wakeford and Daniel Staub are employees of and may own stock/options in Alexion, AstraZeneca Rare Disease. Maria Luisa Brandi has received consulting fees, support for attending meetings, and honoraria from Alexion, AstraZeneca Rare Disease. She is also on the Alexion advisory board and her institution has received grants from Alexion, AstraZeneca Rare Disease. Ethical Approval: This review article did not require institutional review board or institutional animal care and use committee approval, as it is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Similar articles

See all similar articles

References

    1. Högler W, Langman C, da Silva HG, et al. Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry. BMC Musculoskelet Disord. 2019;20(1):80. https://doi.org/10.1186/s12891-019-2420-8 . - DOI - PubMed - PMC
    1. Conti F, Ciullini L, Pugliese G. Hypophosphatasia: clinical manifestation and burden of disease in adult patients. Clin Cases Miner Bone Metab. 2017;14(2):230–4. https://doi.org/10.11138/ccmbm/2017.14.1.230 . - DOI - PubMed - PMC
    1. Weber TJ, Sawyer EK, Moseley S, Odrljin T, Kishnani PS. Burden of disease in adult patients with hypophosphatasia: results from two patient-reported surveys. Metabolism. 2016;65:1522–30. https://doi.org/10.1016/j.metabol.2016.07.006 . - DOI - PubMed
    1. Rathbun JC. Hypophosphatasia; a new developmental anomaly. Am J Dis Child. 1948;75(6):822–31. https://doi.org/10.1001/archpedi.1948.02030020840003 . - DOI
    1. Whyte MP, Rockman-Greenberg C, Ozono K, et al. Asfotase alfa treatment improves survival for perinatal and infantile hypophosphatasia. J Clin Endocrinol Metab. 2016;101(1):334–42. https://doi.org/10.1210/jc.2015-3462 . - DOI - PubMed

LinkOut - more resources