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

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

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1 Citation (Scopus)

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.

Original languageEnglish
JournalJournal of Bone and Mineral Research
DOIs
Publication statusAccepted/In press - 2020

Bibliographical note

Funding Information:
This study was funded by Kyowa Kirin Co., Ltd. We are grateful to the patients who participated in this study, as well as the clinical study coordinators and subinvestigators at the 6 sites (University of Tokyo Hospital, Osaka City University Hospital, Toranomon Hospital, Kobe University Hospital, Severance Hospital, and Seoul National University Hospital). We thank Atsushi Suzuki (Fujita Health University) and Ryo Okazaki (Teikyo University Chiba Medical Center) for reviewing the safety data. We thank Sally‐Anne Mitchell, PhD, of Edanz Medical Writing, for providing medical writing support, which was funded by Kyowa Kirin Co., Ltd., in accordance with Good Publication Practice guidelines ( http://www.ismpp.org/gpp3 ). The data that support the findings of this study are available from the corresponding author upon reasonable request.

Funding Information:
This study was funded by Kyowa Kirin Co., Ltd. We are grateful to the patients who participated in this study, as well as the clinical study coordinators and subinvestigators at the 6 sites (University of Tokyo Hospital, Osaka City University Hospital, Toranomon Hospital, Kobe University Hospital, Severance Hospital, and Seoul National University Hospital). We thank Atsushi Suzuki (Fujita Health University) and Ryo Okazaki (Teikyo University Chiba Medical Center) for reviewing the safety data. We thank Sally-Anne Mitchell, PhD, of Edanz Medical Writing, for providing medical writing support, which was funded by Kyowa Kirin Co., Ltd., in accordance with Good Publication Practice guidelines (http://www.ismpp.org/gpp3). The data that support the findings of this study are available from the corresponding author upon reasonable request. Authors' roles: Study design: SF, SY, MKanematsu, and HK. Study conduct: YI, NI, YR, YTakeuchi, CSS, and YTakahashi. Data analysis: MKojima. Drafting manuscript: YI and HO. Revising manuscript content: NI, YR, YTakeuchi, CSS, YTakahashi, YS, SF, MKanematsu, MKojima, and HK. Approving final version of manuscript: YI. All authors accept responsibility for the integrity of the data analysis.

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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