Regulatory Decision Summary for Crysvita
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
ATC code: M05BX05
Type of submission:
What was the purpose of this submission?
The purpose of this submission was to obtain authorization for Crysvita (burosumab) for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 1 year of age and older. After evaluation of the submitted data package, Health Canada authorized the requested indication.
Why was the decision issued?
X-linked hypophosphatemia is a rare disease affecting approximately 1 in 20,000 people. The disorder is characterized by inadequate levels of phosphorus in the body to undertake normal bone growth and remodeling, resulting in rickets in children and osteomalacia in adults.
Authorization of Crysvita for treatment of X-linked hypophosphatemia was based on 2 clinical trials in pediatric patients aged 1-12 years (n=65) and 5 clinical trials in adults (n=176). One trial in adults had a 24-week double-blind placebo-controlled period, while other trials and extension periods were open label.
In the pediatric population, patients received a range of doses of Crysvita and all patients underwent dose titration towards a target range of serum phosphorus. After 40 weeks of treatment, pediatric patients showed significant improvements in radiographic endpoints (e.g., Rickets Severity Scale) and biomarkers (e.g., alkaline phosphatase).
In adults given 1 mg/kg Crysvita every 4 weeks, there were improvements in serum biomarkers as well as in the healing of fractures and pseudofractures when compared to adults dosed with placebo.
The most common adverse drug reactions in both children and adults were injection site reactions.
The recommended starting dose of Crysvita in pediatric patients is 0.8 mg/kg every 2 weeks, with titration of dose according to the patients serum phosphorus response. In adults, the recommended dose is 1 mg/kg every 4 weeks and dose should be lowered if serum phosphorus is higher than the normal range.
Health Canada granted this submission priority review due to the rarity of the disease and lack of other medications to treat X-linked hypophosphatemia. Authorization was granted based on the totality of evidence from non-clinical, quality, and clinical data that indicated a positive benefit-risk profile for Crysvita (burosumab) use in adults and children aged 1 year and older with X-linked hypophosphatemia.
For more information on Health Canadas decision, please view the Summary Basis of Decision.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.