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ID 116452
Title Alternative
BUROSUMAB IN TUMOR-INDUCED OSTEOMALACIA
Author
Imanishi, Yasuo Osaka City University
Ito, Nobuaki The University of Tokyo
Rhee, Yumie Yonsei University College ofMedicine
Takeuchi, Yasuhiro Toranomon Hospital|Okinaka Memorial Institute for Medical Research
Shin, Chan Soo Seoul National University
Takahashi, Yutaka Kobe University
Onuma, Hiroki Kyowa Kirin
Kojima, Masahiro Kyowa Kirin
Kanematsu, Masanori Kyowa Kirin
Kanda, Hironori Kyowa Kirin
Seino, Yoshiki Japan Community Healthcare Organization
Keywords
CLINICAL TRIALS
OSTEOMALACIA AND RICKETS
PTH/VIT D/FGF23
Content Type
Journal Article
Description
Patients with tumor-induced osteomalacia (TIO), an acquired paraneoplastic condition characterized by osteomalacia due to hypophosphatemia, exhibit a similar clinical picture to those with X-linked hypophosphatemic rickets/osteomalacia (XLH). The human monoclonal anti-fibroblast growth factor 23 (FGF23) antibody burosumab (KRN23) increases serum phosphate and improves bone turnover, fracture healing, pain, and physical function in XLH patients by inhibiting circulating FGF23; thus, burosumab is expected to be an effective treatment for TIO. We report here an interim analysis of a multicenter, open-label, intraindividual dose-adjustment study of burosumab (0.3 to 2.0 mg/kg every 4 weeks) in Japanese and Korean TIO patients. The primary endpoint was the fasting serum phosphate level at each visit. Key secondary endpoints were changes over time in bone biomarkers, pharmacodynamic markers, bone histomorphometric parameters, motor function, and patient-reported outcomes. Safety was assessed based on treatment-emergent adverse events (TEAEs). Thirteen patients received burosumab treatment, of whom 4 underwent bone biopsy. The mean dose after week 112 was approximately 1.0 mg/kg. After the first burosumab administration, mean serum phosphate levels increased and remained above the lower limit of normal and in the normal range from weeks 14 to 112. Bone biomarkers initially increased, reaching maximum values at week 16 or 24, and then gradually decreased. After burosumab treatment, patients were able to walk further (evaluated by the 6-minute walk test), reported decreased pain levels, and showed a tendency toward healing of baseline fractures and pseudofractures. Two patients discontinued, one each due to disease progression and consent withdrawal. Burosumab was generally well tolerated, with no treatment-related TEAEs of grade ≥3 and no treatment-related serious AEs. In conclusion, the interim results of this first study of burosumab to treat TIO patients indicate that this drug has the potential to provide clinical benefit for patients with unresectable tumors. The full study results are eagerly anticipated.
Journal Title
Journal of Bone and Mineral Research
ISSN
15234681
NCID
AA12479704
AA10688587
Publisher
American Society for Bone and Mineral Research|Wiley
Volume
36
Issue
2
Start Page
262
End Page
270
Published Date
2020-09-23
Rights
This is an open access article under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences