Regulatory Decision Summary for Crysvita

Authorization was based on the totality of evidence provided with the submission, which included, a multicenter, randomized, open-label study Phase 3 pivotal trial (UX023-CL301). Patients aged 1 to 12 years with XLH, received either burosumab (n = 29), every 2 weeks, or daily active control (oral phosphate/active vitamin D therapy) (n = 32), for 64 weeks.

The primary efficacy endpoint was the change in rickets at Week 40 as assessed by the radiographic global impression of change (RGI-C) global score. The primary analysis demonstrated superiority of burosumab over active control for the primary endpoint.

There is a need to treat children with XLH as early as possible to decrease the severity of symptoms and prevent permanent damage to the skeleton. Since none of the patients in the current and previous studies was in the age range of 6 months to 1 year, the authorization was based on pharmacologic modelling in support of dosing, beginning at 6 months of age.

The safety profile of burosumab in Study UX023-CL301 was similar to that observed in previous studies in children with XLH, treated with burosumab. The adverse events with the highest proportions (≥30%) were nasopharyngitis, arthralgia, pyrexia, cough, pain in extremity and vomiting. Serious adverse events of craniosynostosis, viral infection and migraine were experienced by one burosumab treated subject each; none of the subjects discontinued from the study or died. Considering that the infant subjects will be monitored frequently by medical specialists, the benefits of burosumab in infants age 6 months to one year were determined to outweigh the risks.