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Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study

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Abstract

Summary

The efficacy and safety of weekly oral odanacatib (ODN) 50 mg for up to 8 years were assessed in postmenopausal women with low bone mineral density (BMD). Treatment with ODN for up to 8 years resulted in continued or maintained increases in BMD at multiple sites and was well tolerated.

Introduction

ODN is a selective inhibitor of cathepsin K. In a 2-year phase 2b study (3/10/25/50 mg ODN once weekly [QW] or placebo) and extensions (50 mg ODN QW or placebo), ODN treatment for 5 years progressively increased BMD and decreased bone resorption markers in postmenopausal women with low BMD (ClinicalTrials.gov NCT00112437).

Methods

In this prespecified interim analysis at year 8 of an additional 5-year extension (years 6 to 10), patients (n = 117) received open-label ODN 50 mg QW plus weekly vitamin D3 (5600 IU) and calcium supplementation as needed. Primary end points were lumbar spine BMD and safety. Patients were grouped by ODN exposure duration.

Results

Mean (95 % confidence interval [CI]) lumbar spine BMD changes from baseline were 4.6 % (2.4, 6.7; 3-year continuous ODN exposure), 12.9 % (8.1, 17.7; 5 years), 12.8 % (10.0, 15.7; 6 years), and 14.8 % (11.0, 18.6; 8 years). Similar patterns of results were observed for BMD of trochanter, femoral neck, and total hip versus baseline. Geometric mean changes from baseline to year 8 for bone resorption markers were approximately −50 % (uNTx/Cr) and −45 % (sCTx), respectively (all groups); bone formation markers remained near baseline levels. No osteonecrosis of the jaw, delayed fracture union, or morphea-like skin reactions were reported.

Conclusions

Treatment with ODN for up to 8 years resulted in gains in BMD at multiple sites. Bone resorption markers remained reduced, with no significant change observed in bone formation markers. Treatment with ODN for up to 8 years was well tolerated.

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Acknowledgments

This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. Medical writing support was provided by Annette Smith, PhD, of Complete Medical Communications, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. Authors’ roles: study design CD, NV, and AL; study conduct CD, AL, and DG; data collection JH, IR, JARP, CD, RK, and DG; data analysis RR, PDM, RK, NV, AL, and DG; data interpretation RR, JH, PDM, CD, RK, NV, AL, and DG; statistical expertise NV and RK; revising manuscript content RR, C-LB, JH, PDM, IR, JARP, CD, RK, NV, AL, and DG; approved final version RR, C-LB, JH, PDM, IR, JARP, CD, RK, NV, AL, and DG; and RK, NV, AL, and DG take responsibility for the integrity of the data analysis.

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Authors and Affiliations

  1. Division of Bone Diseases, Geneva University Hospitals, CH-1211, Geneva 14, Switzerland

    R. Rizzoli

  2. Hopital d’Orléans la Source, Orléans, France

    C.-L. Benhamou

  3. Osteoporoseklinikken, Oslo, Norway

    J. Halse

  4. Colorado Center for Bone Research, University of Colorado Health Sciences Center, Lakewood, CO, USA

    P. D. Miller

  5. University of Auckland, Auckland, New Zealand

    I. R. Reid

  6. Pontificia Universidad Católica de Chile, Santiago, Chile

    J. A. Rodríguez Portales

  7. Merck & Co., Inc., Kenilworth, NJ, USA

    C. DaSilva & D. Gurner

  8. Formerly MSD, Oss, The Netherlands

    R. Kroon

  9. MSD Europe Inc., Brussels, Belgium

    N. Verbruggen

  10. Formerly Merck & Co., Inc., Kenilworth, NJ, USA

    A. T. Leung

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  1. R. Rizzoli
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Corresponding author

Correspondence to R. Rizzoli.

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Conflicts of interest

R. Rizzoli has received fees for board membership from Amgen, Danone, Merck, Servier, and Takeda and lecture fees from Amgen, Danone, GSK, Merck, and Servier. C.-L. Benhamou has received fees for board membership from Rottapharm, Pierre Fabre, Amgen, Novartis, and MSD and grants from Amgen and Servier. J. Halse has received a grant and travel expenses to an investigator meeting from MSD Norway AS for this study and consultancy fees from MSD Norway AS, Eli Lilly Norway AS, grants from Amgen AB Norway, and lecture fees from GSK Norway AS and Amgen AB Norway. P. D. Miller has participated in scientific advisory boards for Alexion, Amgen, AgNovos, Lilly, Merck, Radius Pharma, and Roche and in speaker bureaus for Alexion Pharmaceuticals, Amgen, and Radius Health. He has received research grants from Alexion, Amgen, Boehringer Ingelheim, Immunodiagnostics, Lilly, Merck, Merck Serono, NBHA, Novartis, Novo Nordisk, Radius Pharma, Roche Diagnostics, and Takeda. I.R. Reid has received fees from Merck for consultancy, lectures, and board membership, and his institution has received a grant from Merck for this study. J. A. Rodríguez Portales has received travel expenses to attend an investigator meeting, and his institution has received grants from Merck for this and other studies. C. DaSilva, N. Verbruggen, and D. Gurner are employees of and hold stock/stock options in Merck & Co., Inc. R. Kroon was an employee of MSD at the time of the study. A.T. Leung was an employee of Merck & Co., Inc. at the time of the study and currently holds stocks of the company.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Rizzoli, R., Benhamou, CL., Halse, J. et al. Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study. Osteoporos Int 27, 2099–2107 (2016). https://doi.org/10.1007/s00198-016-3503-0

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  • DOI: https://doi.org/10.1007/s00198-016-3503-0

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