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Efficacy of romosozumab followed by denosumab in women at high risk of fracture

Publish date:: December 4, 2020

Key clinical point: Romosozumab followed by denosumab results in significant bone mineral density (BMD) gains and numerically lower vertebral fractures in postmenopausal Japanese women with osteoporosis at high risk of fracture vs. placebo followed by denosumab through 36 months of follow-up.

Major finding: At 12, 24, and 36 months, the incidence of new vertebral fractures was lower with romosozumab/denosumab vs. placebo/denosumab (relative risk reduction at all timepoints: 84%; P = .056). BMD increase at 12, 24, and 36 months were greater with romosozumab/denosumab vs. placebo/denosumab (lumbar spine: 16.3%, 21.5%, and 23.2% vs. 0.4%, 8.1%, and 10.4%; total hip: 4.9%, 7.9%, and 8.9% vs. 0.4%, 2.8%, and 4.1%; femoral neck: 4.8%, 7.6%, and 8.1% vs. 0.3%, 3.3%, and 3.7%, respectively; all P less than .001).

Study details: This post hoc analysis of phase 3 FRAME study included 187 postmenopausal Japanese women with osteoporosis at high risk of fracture (romosozumab/denosumab group, n = 91; placebo/denosumab group, n = 96).

Disclosures: This study was funded by Amgen Inc., Astellas, and UCB Pharma. A Miyauchi received consulting fees from Amgen, Astellas BioPharma K.K., and Teijin Pharma. E Hamaya, K Nishi, and J Shimauchi are employees of Amgen K.K., Japan, and E Hamaya holds stock in Amgen Inc. W Yang is an employee of Amgen Inc., USA. C Libanati is an employee of UCB Pharma, Belgium, and holds stock in UCB Pharma. C Tolman is an employee of Amgen and holds stock in Amgen.

Commentary

“Romosozumab and denosumab are medications approved for the treatment of osteoporosis. This was a post-hoc analysis of a group of Japanese postmenopausal women with osteoporosis at high risk of fracture (n=187) who participated in the open-blinded phase of FRAME study in which after 12 month of romosozumab 210 mg vs placebo, participants who continued in the study were given denosumab 60 for 12 months, followed by an additional 12 months of denosumab treatment for those who remained in the study. All participants received daily calcium 500–1000 mg and vitamin D 600–800 IU. Endpoints were incidence of new vertebral fracture at 12, 24 and 36 months and percentage change from baseline in bone mineral density (BMD).

There were fewer incident vertebral fractures among the patients in the romosozumab/denosumab group compared to placebo/denosumab group, but the difference was not statistically significant, likely due to the small sample size (p value = 0.056). However, the BMD increases at all three time points were higher in the romosozumab/denosumab group vs placebo/denosumab group. These findings support the use of romosozumab followed by denosumab in patients at high risk of fracture.”