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Interim Analysis of a Phase 2 Open-Label Trial Assessing Burosumab Efficacy and Safety in Patients With Tumor-Induced Osteomalacia

Authors
 Yasuo Imanishi  ;  Nobuaki Ito  ;  Yumie Rhee  ;  Yasuhiro Takeuchi  ;  Chan Soo Shin  ;  Yutaka Takahashi  ;  Hiroki Onuma  ;  Masahiro Kojima  ;  Masanori Kanematsu  ;  Hironori Kanda  ;  Yoshiki Seino  ;  Seiji Fukumoto 
Citation
 JOURNAL OF BONE AND MINERAL RESEARCH, Vol.36(2) : 262-270, 2021-02 
Journal Title
 JOURNAL OF BONE AND MINERAL RESEARCH 
ISSN
 0884-0431 
Issue Date
2021-02
Keywords
CLINICAL TRIALS ; OSTEOMALACIA AND RICKETS ; PTH/VIT D/FGF23
Abstract
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. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
Files in This Item:
T202100530.pdf Download
DOI
10.1002/jbmr.4184
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Rhee, Yumie(이유미) ORCID logo https://orcid.org/0000-0003-4227-5638
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182168
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