Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study

Ki-Hyun Baek, Yoon-Sok Chung, Jung-Min Koh, In Joo Kim, Kyoung Min Kim, Yong-Ki Min, Ki Deok Park, Rajani Dinavahi, Judy Maddox, Wenjing Yang, Sooa Kim, Sang Jin Lee, Hyungjin Cho, Sung-Kil Lim, Ki-Hyun Baek, Yoon-Sok Chung, Jung-Min Koh, In Joo Kim, Kyoung Min Kim, Yong-Ki Min, Ki Deok Park, Rajani Dinavahi, Judy Maddox, Wenjing Yang, Sooa Kim, Sang Jin Lee, Hyungjin Cho, Sung-Kil Lim

Abstract

Background: This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis.

Methods: Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤-2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months.

Results: At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (-0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 N-terminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively.

Conclusion: Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).

Keywords: Bone density; Bone turnover markers; Korea; Randomized controlled trial; Romosozumab.

Conflict of interest statement

CONFLICTS OF INTEREST

Yoon-Sok Chung reports consultancy fee from Amgen, Eli Lilly, MSD, and Yuyu. Rajani Dinavahi, Judy Maddox, and Wenjing Yang are employees and stockholders of Amgen Inc. Sooa Kim, Sang Jin Lee, and Hyungjin Cho are employees of Amgen Korea Limited.

Ki-Hyun Baek, Jung-Min Koh, In Joo Kim, Kyoung Min Kim, Yong-Ki Min, Ki Deok Park, and Sung-Kil Lim do not have any conflicts of interest to declare. This study was sponsored by Amgen Inc. Editorial support, in the form of medical writing, assembling tables and creating high-resolution images based on authors’ detailed directions, collating author comments, copyediting, fact checking, and referencing, was provided by Annirudha Chillar, MD, PhD, and Mami Hirano, MS, of Cactus Life Sciences (part of Cactus Communications) and funded by Amgen Korea.

Figures

Fig. 1
Fig. 1
Study design. IP, investigational product; D, day; M, month; SC, subcutaneous; QM, once monthly.
Fig. 2
Fig. 2
Patient disposition. BMD, bone mineral density; BTM, bone turnover marker.
Fig. 3
Fig. 3
Percent change (least square mean and 95% confidence interval) from baseline in dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck at month 6.
Fig. 4
Fig. 4
Median (interquartile range) percent change from baseline in (A) procollagen type 1 N-terminal propeptide (P1NP) and (B) serum C-terminal telopeptide of type 1 collagen (CTX) by visit. SC, subcutaneous; QM, once monthly.

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