Romosozumab/CDP7851 for the treatment of osteoporosis

Abstract

Osteoporosis is an important worldwide health problem, conferring significant costs on healthcare. Current osteoporosis therapies are anti-resorptive and have proven anti-fracture efficacy, while there is a paucity of osteoanabolic therapies. Romosozumab is a humanized monoclonal antibody against sclerostin, an inhibitor of osteoblastic activity. Two-year follow-up data from initial clinical studies show rapid and robust increases in bone mineral density at all sites, except the wrist. Significant increases in bone formation markers have also been observed after administration of romosozumab. Notably, and unprecedented among any currently available therapy, this increase in bone formation is accompanied with control of bone resorption, allowing an enhanced anabolic potential compared with the only other currently available anabolic therapy, teriparatide. Romosozumab has been well tolerated in initial studies and its effects on BMD are augmented by follow-on anti-resorptive therapy. Ongoing Phase III studies will provide data regarding anti-fracture efficacy and comparisons with alendronate, as well as longer-term safety.

Keywords:

• anabolic therapy
• CDP7851
• monoclonal antibody
• romosozumab
• sclerostin

Financial & competing interests disclosure

The authors were supported by Monash University and National Health and Medical Research Council of Australia. PR Ebeling has received research funding from Amgen, Merck, Novartis, and Eli-Lilly and honoraria from Merck, Amgen, Pfizer, ViiV Healthcare, and GlaxoSmithKline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Romosozumab is a humanized monoclonal antibody against sclerostin.

• Its subcutaneous administration is associated with a rapid increase in BMD at all sites, except the radius.

• Bone turnover markers support the anabolic action of romosozumab, with significant increases in P1NP after administration, with an associated control of bone resorption.

• Romosozumab was well tolerated in Phase I and II clinical studies.

• Ongoing Phase III studies will provide data regarding anti-fracture efficacy and long-term safety, as well as informing the optimal therapeutic regimen and any potential role for its combination with existing osteoporosis therapies.

Notes