Crysvita · X-linked dominant hypophosphataemic rickets in children and adolescents - first-line
Development and Regulatory status
Jan 19: Crysvita 10mg/ml soln for inj in vial cost is £2,992/vial .
Jan 19: Launched in UK .
Apr 18: Launched in US .
Apr 18: In the US, Ultragenyx will price burosumab at $160,000 per year in children and $200,000 per year for adults after rebates and discounts .
Apr 18: Approved in US .
Feb 18: Marketing authorisation granted throughout the EU by the EMA .
Dec 17: recommended for approval in the EU, for use in children and adolescents. The full indication is "for the treatment of X-linked hypophosphataemia with radiographic evidence of bone disease in children 1 year of age and older and adolescents with growing skeletons." It is proposed that it should be administered only by relevant specialists .
Oct 17: BLA accepted for priority review by FDA. Prescription Drug User Fee Act (PDUFA) action date is 17/04/18 .
Aug 17: Ultragenyx and Kyowa Hakko Kirin have announced that they have submitted the Biologics License Application (BLA) to the FDA - the FDA now has 60 days to decide whether to accept the submission, and if it does so it will then set an action date for a decision 
Jun 17: Ultragenyx has reached agreement with the FDA on the clinical package to support the burosumab (KRN23) BLA filing for XLH. The FDA agreed that the BLA can be submitted based on available clinical data and confirmed that both pediatric and adult indications would be included in the review. Based on the agreement, submission is planned for H2 17 .
Jan 17: The EMA has accepted for review the Marketing Authorisation Application (MAA) for KRN23 for the treatment of X-linked hypophosphatemia . /
Trial or other data
Dec 17: Ultragenyx announce further results form NCT01340482. Patients treated with burosumab for 48 weeks had sustained maintenance of normal serum phosphorus levels and further improvement in stiffness, physical function and pain .
Apr 17: Ultragenyx announces positive PIII results. The trial enrolled 134 adults, who were randomised to receive a 1mg/kg dose of burosumab every 4 weeks or a placebo over a 24-week study period. Data from that final timepoint show that normal range serum phosphorus levels were achieved in 94% of patients on burosumab, compared with just 8% in the placebo arm. Measures of clinical symptoms of XLH such as stiffness and physical functioning also favored burosumab, with statistical improvements over control, while there was a trend toward an improvement in pain levels with burosumab. Taken together, that equated to a meaningful improvement in symptom scores that seemed to be sustained after the study period. There was also evidence for improved bone formation with burosumab suggesting that healing is starting to occur. Patients will be followed up on through 48 weeks of treatment .
NCT01340482 - an open-label, uncontrolled phase I/II trial to assess the safety and efficacy of multiple, escalating doses completed October 2013. Patients were dosed every 28 days, up to four doses. Results presented at the Joint meeting of the 16th International Society of Endocrinology and the 96th Annual Meeting of the Endocrine Society 2014. A 12-month, open-label extension phase I/II trial was initiated in February 2012 (NCT01571596). The study enrolled 23 patients from the US and Canada. Cumulative results from these 2 trials were presented at the Annual Meeting of the American Society of Bone and Mineral Research in September 2014. Imel EA, et al. Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23. J Clin Endocrinol Metab. 2015 Jul;100(7):2565-73. doi: 10.1210/jc.2015-1551. Epub 2015 Apr 28. PIIb extension study to evaluate the long-tern safety and pharmacodynamics started Dec 2014 (NCT02312687) enrolling subjects who participated in the above studies.