dm+d

35821711000001104

New Medicines

Crysvita X-linked hypophosphatasia in adults

Information

Crysvita
Licence extension / variation
Kyowa Kirin
Ultragenyx

Development and Regulatory status

Launched
Launched
Launched
October 2020
Yes
Yes
Jul 21Approved in the EU for self-administration [7].
May 21Positive CHMP approval for self-administered burosumab for treatment of hypophosphatemia. Currently, burosumab SC injection requires administration by a HCP. If approved, patients on a stable dose can be considered for self-administration, with first self-administered dose being supervised by a HCP [6].
Oct 20Approved in EU [5]
Jul 20Recommended for EU approval by CHMP - the amended indication is "for the treatment of X-linked hypophosphataemia, in children and adolescents aged 1 to 17 years with radiographic evidence of bone disease, and in adults" [4].
Jun 20Currently pre-registration in EU. Already approved in US [2,3].
Oct 14Granted orphan drug status in EU (EU/3/14/1351) [2].

Category

Recombinant IgG1 monoclonal antibody
X-linked hypophosphatemia (XLH) is the most common form of heritable rickets and osteomalacia with a prevalence of approximately 1/ 20,000.
X-linked hypophosphatasia in adults
Subcutaneous injection

Further information

Yes

Trial or other data

Sep 21Results from PIII NCT02526160 show burosumab treatment is associated with significant improvements in patient reported outcomes after 96 weeks, including ambulatory function [8]. Results are published in RMD Open [9].
Jun 20Five trials are relevant to this indication: PI/II (NCT01340482) open-label, repeat-dose, dose-escalation study of KRN23 in adults with XLH; PII (NCT01571596 and NCT02312687) extension studies; PIII (NCT02537431) open-label, single-arm study to evaluate the effects of KRN23 on osteomalacia in adults with XLH; PIII (NCT02526160) randomised, double-blind, placebo-controlled study with open-label extension to assess the efficacy and safety of KRN23 in adults with XLH [1,2].

Evidence based evaluations

Information

Crysvita
Licence extension / variation
Kyowa Kirin
Ultragenyx

Development and Regulatory status

None
None
Launched
Yes
Yes
Jun 20Approved by the FDA on the basis of results from the two PII studies [4].
Apr 18Orphan drug status granted in EU (EU/3/18/2011) [3].

Category

Binds to and inhibits the biological activity of fibroblast growth factor 23 (FGF23) thereby increasing renal tubular reabsorption of phosphate and serum concentrations of phosphate and 1,25 dihydroxy-Vitamin D.
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In 2011, it was reported that over 200 cases had been reported in the last 10 years indicates a growing recognition of this disease [1].
FGF23-related hypophosphataemia in adults with tumour-induced osteomalacia
Subcutaneous injection

Further information

Yes

Trial or other data

Sep 20PII study (NCT02722798) is active but no longer recruiting [2].
Aug 20PII study (NCT02304367) is active but no longer recruiting [2].
Apr 16PII study to evaluate the efficacy and safety of KRN23 after its 48-week once every 4 weeks repeated subcutaneous administration to Japanese and Korean patients with Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome by a multicenter, open-label, intraindividual dose adjustment study starts (NCT02722798). 6 subjects will be recruited in Japan and South Korea. Collection of primary outcome data (serum phosphorus concentration up to week 48) due to complete Jul 17 [2].
Mar 15PII study to evaluate the effect of burosumab treatment on increasing serum phosphorus levels in adults with TIO or ENS-associated osteomalacia, and to evaluate improvement in TIO/epidermal nevus syndrome (ENS)-associated osteomalacia as determined by osteoid thickness (O.Th), osteoid surface/bone surface (OS/BS), osteoid volume/bone volume (OV/BV) and mineralization lag time (MLt) starts (NCT02304367). 17 patients will be recruited in the US. Participants will receive burosumab at a starting dose of 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may have been titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W) in order to achieve fasting peak serum phosphorus levels within the target range of 2.5 to 4.0 mg/dL. Collection of primary outcome data due to complete Jul 17 [2].

Evidence based evaluations