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Targeting Sclerostin in Postmenopausal Osteoporosis: Focus on Romosozumab and Blosozumab

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Abstract

Most current treatments for osteoporosis inhibit bone resorption and reduce total fracture numbers by about one-quarter. The identification of the osteocytic protein sclerostin as a potent regulator of bone turnover and bone density has led to the development of a new therapeutic class—agents that inhibit sclerostin activity, resulting in increased bone formation and reduced bone resorption. Romosozumab and blosozumab are monoclonal antibodies that bind to sclerostin, reducing its inhibition of Wnt signaling. They have comparable activities in phase I and II studies, doubling formation markers, halving resorption indices, and increasing spine bone density by >10% over 12 months. Only romosozumab has progressed to phase III, where the first study showed a 73% reduction in vertebral fracture risk and a 36% reduction in clinical fractures at 1 year. It was well-tolerated. A further phase III study will conclude in 2017. Romosozumab is a very promising medication in the management of established osteoporosis, but much remains to be done to determine its optimal duration and sequence of administration.

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Notes

  1. On May 21, 2017 Amgen and UCB announced that the second phase III study of romosozumab (the ARCH study) met both primary endpoints and the key secondary endpoint. At the primary analysis, treatment with romosozumab for 12 months followed by alendronate significantly reduced the incidence of new vertebral fractures through 24 months, clinical fractures (primary endpoints) and non-vertebral fractures (key secondary endpoint) in postmenopausal women with osteoporosis at high risk for fracture, compared with alendronate alone. There was a nominally significant reduction in hip fractures. An imbalance in positively adjudicated cardiovascular serious adverse events was observed as a new safety signal (2.5% romosozumab versus 1.9% alendronate at 12 months). http://www.prnewswire.com/news-releases/amgen-and-ucb-announce-top-line-phase-3-data-from-active-comparator-study-of-evenity-romosozumab-in-postmenopausal-women-with-osteoporosis-300461160.html.

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Authors and Affiliations

  1. Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand

    Ian R. Reid

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  1. Ian R. Reid
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Correspondence to Ian R. Reid.

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Conflicts of interest

IRR has received research support and/or acted as a consultant for Novartis, Merck, Lilly, and Amgen.

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Supported by the Health Research Council of New Zealand.

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Reid, I.R. Targeting Sclerostin in Postmenopausal Osteoporosis: Focus on Romosozumab and Blosozumab. BioDrugs 31, 289–297 (2017). https://doi.org/10.1007/s40259-017-0229-2

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