Findings from a phase 3 study have shown that the investigational agent romosozumab (Amgen/UCB) significantly reduced the incidence of new vertebral fractures in postmenopausal women with osteoporosis through 12 and 24 months, meeting the study’s co-primary endpoints. The results from this study, the first to evaluate fracture risk reduction as early as one year after treatment as a primary endpoint, were published in the New England Journal of Medicine.
Romosozumab works by binding to and inhibiting the activity of the protein sclerostin. As a result, the treatment has a dual effect on bone, both increasing bone formation and decreasing bone breakdown.
The FRActure Study in Postmenopausal WoMen With OstEoporosis (FRAME), which enrolled 7,180 women, showed that subjects randomly assigned to receive monthly subcutaneous romosozumab (210 mg) experienced a statistically significant 73% reduction in the relative risk of a new vertebral fracture through 12 months (the first co-primary endpoint) compared with those receiving placebo (fracture incidence: 0.5% vs. 1.8%, respectively; P < 0.001). The data also showed that by six months, new vertebral fractures occurred in 14 romosozumab-treated patients compared with 26 placebo-treated patients, and that between six and 12 months, fractures occurred in two additional romosozumab-treated patients compared with 33 additional placebo-treated patients.
For those patients who received romosozumab during the first year of the study, fracture risk reduction persisted through month 24 after both groups transitioned to denosumab treatment during the second year of the study; there was a statistically significant 75% reduction in the risk of vertebral fracture at month 24 (the other co-primary endpoint) in patients who received romosozumab followed by denosumab compared with those given placebo followed by denosumab (fracture incidence: 0.6% vs. 2.5%, respectively; P <0.001). During the second year of the study, new vertebral fractures occurred in five patients who transitioned from romosozumab to denosumab and in 25 patients who transitioned from placebo to denosumab.
Patients receiving romosozumab experienced a statistically significant 36% reduction in the relative risk of a clinical fracture (a secondary endpoint) through 12 months compared with those receiving placebo (fracture incidence: 1.6% vs. 2.5%, respectively; P = 0.008). Clinical fractures were defined as all symptomatic fractures (both nonvertebral and painful vertebral fractures). A 33% reduction in the relative risk of a clinical fracture was observed through 24 months after patients transitioned from romosozumab to denosumab compared with patients that transitioned from placebo to denosumab (nominal P = 0.002; adjusted P = 0.096).
Treatment with romosozumab resulted in a 25% reduction compared with placebo in the relative risk of nonvertebral fractures through month 12 (another secondary endpoint), but the reduced risk was not statistically significant (fracture incidence: 1.6% vs. 2.1%, respectively; P = 0.096).
In a substudy of 126 subjects, romosozumab increased bone mineral density (BMD), with gains of 9.7% and 4.7% from baseline by six months at the lumbar spine and total hip, respectively, and with gains of 13.3% and 6.8% at 12 months, respectively (P <0.001 for all comparisons vs. placebo). BMD continued to increase in the romosozumab group after patients transitioned to denosumab, reaching 17.6% and 8.8% increases from baseline at the lumbar spine and total hip, respectively, at 24 months (P < 0.001 compared with the placebo-to-denosumab group for all comparisons).
Source: Amgen; September 18, 2016.