EOS789, a broad-spectrum inhibitor of phosphate transport, is safe with an indication of efficacy in a phase 1b randomized crossover trial in hemodialysis patients

Kathleen M. Hill Gallant, Elizabeth Stremke, Laurie L. Trevino, Ranjani N. Moorthi, Simit Doshi, Meryl E. Wastney, Nozomi Hisada, Jotaro Sato, Yoshitaka Ogita, Naohisa Fujii, Yuya Matsuda, Takei Kake, Sharon M. Moe

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1 Scopus citations


The treatment of hyperphosphatemia remains challenging in patients receiving hemodialysis. This phase 1b study assessed safety and efficacy of EOS789, a novel pan-inhibitor of phosphate transport (NaPi-2b, PiT-1, PiT-2) on intestinal phosphate absorption in patients receiving intermittent hemodialysis therapy. Two cross-over, randomized order studies of identical design (ten patients each) compared daily EOS789 50 mg to placebo with meals and daily EOS789 100 mg vs EOS789 100 mg plus 1600 mg sevelamer with meals. Patients ate a controlled diet of 900 mg phosphate daily for two weeks and began EOS789 on day four. On day ten, a phosphate absorption testing protocol was performed during the intradialytic period. Intestinal fractional phosphate absorption was determined by kinetic modeling of serum data following oral and intravenous doses of 33Phosphate (33P). The results demonstrated no study drug related serious adverse events. Fractional phosphate absorption was 0.53 (95% confidence interval: 0.39,0.67) for placebo vs. 0.49 (0.35,0.63) for 50 mg EOS789; and 0.40 (0.29,0.50) for 100 mg EOS789 vs. 0.36 (0.26,0.47) for 100 mg EOS789 plus 1600 mg sevelamer (all not significantly different). The fractional phosphate absorption trended lower in six patients who completed both studies with EOS789 100 mg compared with placebo. Thus, in this phase 1b study, EOS789 was safe and well tolerated. Importantly, the use of 33P as a sensitive and direct measure of intestinal phosphate absorption allows specific testing of drug efficacy. The effectiveness of EOS789 needs to be evaluated in future phase 2 and phase 3 studies.

Original languageEnglish (US)
Pages (from-to)1225-1233
Number of pages9
JournalKidney international
Issue number5
StatePublished - May 1 2021
Externally publishedYes

Bibliographical note

Funding Information:
This study was presented at the 2019 American Society of Nephrology meeting. This study was funded by Chugai. We thank the patients, dietitians, and nurses of the clinical research center, Indiana University Radiation Safety, Indiana University Health Investigational Pharmacy, and Indiana Clinical and Translational Science Institute, for their support. We also thank Dr. Athos Gianella-Borradori (Chugai at the time of the study) for comments. SMM, KMHG, NH, YO, and TK designed the study. SMM, KMHG, ES, LT, RNM, and SD carried out the human subject interventions. SMM, KMHG, MEW, NH, JS, NF, YM, and TK analyzed the data. KMHG, NH, and JS made the figures. KMHG and SMM drafted the manuscript. All of the authors edited and approved the final version of the manuscript.

Funding Information:
SMM receives consulting fees from Amgen and Ardelyx and grant support from Chugai (for this study) and Keryx/Akebia. All grants were paid directly to Indiana University. NH, TK, YO, NF, YM, and JS are employees of Chugai. This publication was made possible with partial salary support of KMHG (principal investigator) from the National Institutes of Health (NIH) grant K01DK102864 and partial salary support of ERS and the CRC from NIH grant UL1TR002529 (principal investigator, A. Shekhar).

Publisher Copyright:
© 2020 International Society of Nephrology


  • hemodialysis
  • intestine
  • phosphorus absorption
  • phosphorus radiotracer
  • sodium-phosphate cotransporters

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Clinical Trial, Phase I
  • Randomized Controlled Trial


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