Skip to main content
Journal cover image

Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23.

Publication ,  Journal Article
Imel, EA; Zhang, X; Ruppe, MD; Weber, TJ; Klausner, MA; Ito, T; Vergeire, M; Humphrey, JS; Glorieux, FH; Portale, AA; Insogna, K; Peacock, M ...
Published in: J Clin Endocrinol Metab
July 2015

CONTEXT: In X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmP/GFR) and serum inorganic phosphorus (Pi), resulting in rickets and/or osteomalacia. OBJECTIVE: The objective was to test the hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve serum Pi in adults with XLH. DESIGN: Two sequential open-label phase 1/2 studies were done. SETTING: Six academic medical centers were used. PARTICIPANTS: Twenty-eight adults with XLH participated in a 4-month dose-escalation study (0.05-0.6 mg/kg); 22 entered a 12-month extension study (0.1-1 mg/kg). INTERVENTION: KRN23 was injected sc every 28 days. MAIN OUTCOME MEASURE: The main outcome measure was the proportion of subjects attaining normal serum Pi and safety. RESULTS: At baseline, mean TmP/GFR, serum Pi, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were 1.6 ± 0.4 mg/dL, 1.9 ± 0.3 mg/dL, and 36.6 ± 14.3 pg/mL, respectively. During dose escalation, TmP/GFR, Pi, and 1,25(OH)2D increased, peaking at 7 days for TmP/GFR and Pi and at 3-7 days for 1,25(OH)2D, remaining above (TmP/GFR, Pi) or near [1,25(OH)2D] pre-dose levels at trough. After each of the four escalating doses, peak Pi was between 2.5 and 4.5 mg/dL in 14.8, 37.0, 74.1, and 88.5% of subjects, respectively. During the 12-month extension, peak Pi was in the normal range for 57.9-85.0% of subjects, and ≥25% maintained trough Pi levels within the normal range. Serum Pi did not exceed 4.5 mg/dL in any subject. Although 1,25(OH)2D levels increased transiently, mean serum and urinary calcium remained normal. KRN23 treatment increased biomarkers of skeletal turnover and had a favorable safety profile. CONCLUSIONS: Monthly KRN23 significantly increased serum Pi, TmP/GFR, and 1,25(OH)2D in all subjects. KRN23 has potential for effectively treating XLH.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

July 2015

Volume

100

Issue

7

Start / End Page

2565 / 2573

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Recombinant Proteins
  • Phosphorus
  • Middle Aged
  • Male
  • Immunoglobulin G
  • Humans
  • Glomerular Filtration Rate
  • Fibroblast Growth Factors
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Imel, E. A., Zhang, X., Ruppe, M. D., Weber, T. J., Klausner, M. A., Ito, T., … Carpenter, T. O. (2015). Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23. J Clin Endocrinol Metab, 100(7), 2565–2573. https://doi.org/10.1210/jc.2015-1551
Imel, Erik A., Xiaoping Zhang, Mary D. Ruppe, Thomas J. Weber, Mark A. Klausner, Takahiro Ito, Maria Vergeire, et al. “Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23.J Clin Endocrinol Metab 100, no. 7 (July 2015): 2565–73. https://doi.org/10.1210/jc.2015-1551.
Imel EA, Zhang X, Ruppe MD, Weber TJ, Klausner MA, Ito T, 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.
Imel, Erik A., et al. “Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23.J Clin Endocrinol Metab, vol. 100, no. 7, July 2015, pp. 2565–73. Pubmed, doi:10.1210/jc.2015-1551.
Imel EA, Zhang X, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey JS, Glorieux FH, Portale AA, Insogna K, Peacock M, Carpenter TO. Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23. J Clin Endocrinol Metab. 2015 Jul;100(7):2565–2573.
Journal cover image

Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

July 2015

Volume

100

Issue

7

Start / End Page

2565 / 2573

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Recombinant Proteins
  • Phosphorus
  • Middle Aged
  • Male
  • Immunoglobulin G
  • Humans
  • Glomerular Filtration Rate
  • Fibroblast Growth Factors