Burosumab Improves Osteomalacia in Adults With X-Linked Hypophosphataemia

April 9, 2019

By Jill Stein

PARIS -- April 8, 2019 -- Burosumab significantly reduces measures of osteomalacia in adults with X-linked hypophosphataemia (XLH), according to results of a phase 3, open-label, single-arm study reported here on April 5 at the 2019 World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO).

In this ongoing study, investigators administer subcutaneous burosumab (1.0 mg/kg) every 4 weeks for 48 weeks to adults with XLH who have not received conventional oral phosphate and vitamin D replacement therapy within 2 years of enrollment.

Thirteen of 14 current study participants completed 48 weeks, and 11 completed paired biopsies. At baseline, 5 patients had severe osteomalacia, and 6 patients had mild osteomalacia. All patients had enthesopathy.

Lead author Peter Kamenicky, MD, PhD, Kremlin-Bicêtre Hospital, Paris, France, noted that, at week 48, all osteomalacia-related histomorphometric measures improved significantly: percent change: osteoid volume/bone volume -54%, osteoid thickness -32%, osteoid surface/bone surface -26%, and mineralisation lag time -52%.

Mean serum phosphorus concentration, averaged across the mid-point of the dose cycle between weeks 0 to 24 increased by 48%, consistent with prior findings.

Markers of bone remodeling increased at week 48, with a least-squares mean increase of 77% in procollagen type 1 N propeptide and 36% in C-terminal telopeptide 1 collagen CTx (both P

Of 4 active pseudofractures detected at baseline, 3 had healed at week 48 and 1 image was missing.

There were significant reductions in pain and global fatigue.

Dr. Kamenicky noted that standard therapy demonstrates some improvement of histomorphometric parameters of osteomalacia, but not normalisation.

He observed that the safety profile of burosumab was similar to that seen in larger randomised clinical trials, with most adverse events of mild to moderate severity.

XLH in adults is characterised by hyophosphataemia, osteomalacia, musculoskeletal pain, stiffness, fractures, pseudofractures, osteoarthritis, enthesopathy, muscle dysfunction, and impaired physical function.

Burosumab is a fully human monoclonal antibody that inhibits the function of fibroblast growth factor-23 and is approved by the US Food and Drug Administration for XLH.

Funding for the study was provided by Ultragenyx Pharmaceutical Inc., Novato, California, manufacturers of burosumab.

[Presentation title: Effect of Burosumab (KRN23), A Fully Human Anti-FGF23 Monoclonal Antibody on Osteomalacia in Adults with X-Linked Hypophosphataemia. Abstract P442]