Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period

Anthony A. Portale, Thomas O. Carpenter, Maria Luisa Brandi, Karine Briot, Hae Ii Cheong, Martine Cohen-Solal, Rachel Crowley, Suzanne M Jan De Beur, Richard Eastell, Yasuo Imanishi, Erik A. Imel, Steven Ing, Nobuaki Ito, Muhammad Javaid, Peter Kamenicky, Richard Keen, Takuo Kubota, Robin Lachmann, Farzana Perwad, Pisit PitukcheewanontStuart H. Ralston, Yasuhiro Takeuchi, Hiroyuki Tanaka, Thomas J. Weber, Han Wook Yoo, Lin Zhang, Christina Theodore-Oklota, Matt Mealiffe, Javier San Martin, Karl Insogna

Research output: Contribution to journalArticle

Abstract

Burosumab, a fully human monoclonal antibody to FGF23, is the only approved treatment for X-linked hypophosphatemia (XLH), a rare genetic disorder characterized by renal phosphate wasting and substantial cumulative musculoskeletal morbidity. During an initial 24-week randomized, controlled trial, 134 adults with XLH received burosumab 1 mg/kg (n = 68) or placebo (n = 66) every 4 weeks. After 24 weeks, all subjects received open-label burosumab until week 48. This report describes the efficacy and safety of burosumab during the open-label treatment period. From weeks 24–48, serum phosphorus concentrations remained normal in 83.8% of participants who received burosumab throughout and were normalized in 89.4% who received burosumab after placebo. By week 48, 63.1% of baseline fractures/pseudofractures healed fully with burosumab, compared with 35.2% with burosumab after placebo. In both groups, burosumab was associated with clinically significant and sustained improvement from baseline to week 48 in scores for patient-reported outcomes of stiffness, pain, physical function, and total distance walked in 6 min. Rates of adverse events were similar for burosumab and placebo. There were no fatal adverse events or treatment-related serious adverse events. Nephrocalcinosis scores did not change from baseline by more than one grade at either week 24 or 48. These data demonstrate that in participants with XLH, continued treatment with burosumab is well tolerated and leads to sustained correction of serum phosphorus levels, continued healing of fractures and pseudofractures, and sustained improvement in key musculoskeletal impairments.

Original languageEnglish (US)
JournalCalcified Tissue International
DOIs
StatePublished - Jan 1 2019

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Familial Hypophosphatemic Rickets
Placebos
Phosphorus
Nephrocalcinosis
Inborn Genetic Diseases
Fracture Healing
Therapeutics
Serum
Randomized Controlled Trials
Phosphates
Monoclonal Antibodies
Morbidity
Kidney
Safety
Pain

Keywords

  • Burosumab
  • FGF23
  • Osteomalacia
  • Vitamin D
  • X-linked hypophosphatemia (XLH)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

Cite this

Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia : Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period. / Portale, Anthony A.; Carpenter, Thomas O.; Brandi, Maria Luisa; Briot, Karine; Cheong, Hae Ii; Cohen-Solal, Martine; Crowley, Rachel; Jan De Beur, Suzanne M; Eastell, Richard; Imanishi, Yasuo; Imel, Erik A.; Ing, Steven; Ito, Nobuaki; Javaid, Muhammad; Kamenicky, Peter; Keen, Richard; Kubota, Takuo; Lachmann, Robin; Perwad, Farzana; Pitukcheewanont, Pisit; Ralston, Stuart H.; Takeuchi, Yasuhiro; Tanaka, Hiroyuki; Weber, Thomas J.; Yoo, Han Wook; Zhang, Lin; Theodore-Oklota, Christina; Mealiffe, Matt; San Martin, Javier; Insogna, Karl.

In: Calcified Tissue International, 01.01.2019.

Research output: Contribution to journalArticle

Portale, AA, Carpenter, TO, Brandi, ML, Briot, K, Cheong, HI, Cohen-Solal, M, Crowley, R, Jan De Beur, SM, Eastell, R, Imanishi, Y, Imel, EA, Ing, S, Ito, N, Javaid, M, Kamenicky, P, Keen, R, Kubota, T, Lachmann, R, Perwad, F, Pitukcheewanont, P, Ralston, SH, Takeuchi, Y, Tanaka, H, Weber, TJ, Yoo, HW, Zhang, L, Theodore-Oklota, C, Mealiffe, M, San Martin, J & Insogna, K 2019, 'Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period', Calcified Tissue International. https://doi.org/10.1007/s00223-019-00568-3
Portale, Anthony A. ; Carpenter, Thomas O. ; Brandi, Maria Luisa ; Briot, Karine ; Cheong, Hae Ii ; Cohen-Solal, Martine ; Crowley, Rachel ; Jan De Beur, Suzanne M ; Eastell, Richard ; Imanishi, Yasuo ; Imel, Erik A. ; Ing, Steven ; Ito, Nobuaki ; Javaid, Muhammad ; Kamenicky, Peter ; Keen, Richard ; Kubota, Takuo ; Lachmann, Robin ; Perwad, Farzana ; Pitukcheewanont, Pisit ; Ralston, Stuart H. ; Takeuchi, Yasuhiro ; Tanaka, Hiroyuki ; Weber, Thomas J. ; Yoo, Han Wook ; Zhang, Lin ; Theodore-Oklota, Christina ; Mealiffe, Matt ; San Martin, Javier ; Insogna, Karl. / Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia : Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period. In: Calcified Tissue International. 2019.
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AU - Brandi, Maria Luisa

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AU - Crowley, Rachel

AU - Jan De Beur, Suzanne M

AU - Eastell, Richard

AU - Imanishi, Yasuo

AU - Imel, Erik A.

AU - Ing, Steven

AU - Ito, Nobuaki

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AU - Tanaka, Hiroyuki

AU - Weber, Thomas J.

AU - Yoo, Han Wook

AU - Zhang, Lin

AU - Theodore-Oklota, Christina

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AU - San Martin, Javier

AU - Insogna, Karl

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N2 - Burosumab, a fully human monoclonal antibody to FGF23, is the only approved treatment for X-linked hypophosphatemia (XLH), a rare genetic disorder characterized by renal phosphate wasting and substantial cumulative musculoskeletal morbidity. During an initial 24-week randomized, controlled trial, 134 adults with XLH received burosumab 1 mg/kg (n = 68) or placebo (n = 66) every 4 weeks. After 24 weeks, all subjects received open-label burosumab until week 48. This report describes the efficacy and safety of burosumab during the open-label treatment period. From weeks 24–48, serum phosphorus concentrations remained normal in 83.8% of participants who received burosumab throughout and were normalized in 89.4% who received burosumab after placebo. By week 48, 63.1% of baseline fractures/pseudofractures healed fully with burosumab, compared with 35.2% with burosumab after placebo. In both groups, burosumab was associated with clinically significant and sustained improvement from baseline to week 48 in scores for patient-reported outcomes of stiffness, pain, physical function, and total distance walked in 6 min. Rates of adverse events were similar for burosumab and placebo. There were no fatal adverse events or treatment-related serious adverse events. Nephrocalcinosis scores did not change from baseline by more than one grade at either week 24 or 48. These data demonstrate that in participants with XLH, continued treatment with burosumab is well tolerated and leads to sustained correction of serum phosphorus levels, continued healing of fractures and pseudofractures, and sustained improvement in key musculoskeletal impairments.

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