Five year data showing the efficacy and safety of Strensiq (asfotase alfa) to treat children with hypophosphatasia (HPP) was published this week in the Journal of Clinical Investigations
. And the long term effects of the drug are very impressive with this otherwise, devastating disease that can afflict horrible bone and muscle pain on the young patients.
Hypophosphatasia (HPP) is a metabolic disorder caused by loss-of-function mutations in the gene that encodes tissue-nonspecific alkaline phosphatase. Poor bone mineralization, a key feature of HPP, can lead to rickets. Other symptoms may include seizures, respiratory compromise, poor growth, and delayed gross motor function.
In 2015, Strensiq (asfotase alfa) was approved as a first-in-class bone-targeted enzyme-replacement therapy for HPP. The approval was based on data from 4 clinical trials, including an open-label phase 2 study in children with hypophosphatasia receiving the drug.
Following that pivotal 6-month study, 12 of the 13 patients entered an extension study that has now continued for 4.5 years with the children receiving asfotase alfa, generally 6 mg/kg/week.
The primary endpoint was skeletal radiographic changes. As shown in Figure 1 below, the median Radiographic Global Impression of Change (RGI-C) scores were significantly superior to historical controls at both 6 months and 2 years. These improvements continued for over 5 years. As shown in the table, Rickets Severity Scores decreased over 5 years of treatment.
Figure 1. Skeletal improvements during treatment with asfotase alfa. Changes in RGI-C scores during 6 months and 2 years of treatment with asfotase alfa. Individual dots illustrate the distribution of individual patient scores at each time point. Boxes represent the median RGI-C scores and represent first and third quartiles. Whisker lines above and below the boxes represent the end-range of patient scores. The RGI-C is scored on a scale ranging from –3 to +3, with 0 representing no change. Negative values represent worsening, and positive values represent improvement or healing. A score of +3 indicates nearly complete or complete healing. Median RGI-C scores for the historical controls and asfotase alfa were 0 and 2, respectively, at 6 months and 2 years. The number of patients assessed at each time point is shown below each bar. P ≤ 0.0001 by Wilcoxon signed-rank test at all time points compared with no change.
Table 1. Change in RSS scores with asfotase alfa treatment
To illustrate the changes in the patients’ skeletal health, the paper included radiographs of one of the patients over time.
Figure 2. Representative radiographic changes. Radiographic changes were documented in 12 treated patients and are illustrated in the Supplemental Methods. Patient 7, a 6-year-old boy at enrollment, is shown. RGI-C, Radiographic Global Impression of Change; RSS, Rickets Severity Score. Note the improvements at 6 months of treatment that persist after 5 years of therapy.
Additional significant improvements were observed with patient growth, strength, motor function, agility, and quality of life.
Generally, the drug was well tolerated although injection site reactions were common and sometimes associated with lipohypertrophy.
Whyte MP, Madson KL, Phillips D, et al. Asfotase alfa therapy for children with hypophosphatasia. JCI Insight
Figures obtained from Whyte et al (2016) which is an open source article.