FROM NEW ENGLAND JOURNAL OF MEDICINE
Results from a large, manufacturer-sponsored, international trial show that romosozumab, a monoclonal antibody against sclerostin, reduced incidence of vertebral fractures by 73% over placebo in women with osteoporosis at 12 months of treatment, and by 75% at 24 months after patients were switched to another biologic agent, denosumab, for the second year of treatment.
Felicia Cosman, MD , of Helen Hayes Hospital in West Haverstraw, N.Y., and Columbia University, New York, and her colleagues randomized 7,180 postmenopausal women with osteoporosis (but without a history of hip fracture, metabolic bone disease, or severe or recurrent vertebral fractures) in the Fracture Study in Postmenopausal Women with Osteoporosis ( FRAME ) trial to 1 year of treatment with 210 mg romosozumab, administered monthly via subcutaneous injection, or sham injection. Romosozumab is an investigational agent that binds and inhibits the activity of the protein sclerostin, increasing bone formation and decreasing bone breakdown.
Of 3,321 patients in the romosozumab arm, 16 (0.5%) experienced a new vertebral fracture at 12 months, compared with 59 (1.8%) of 3,322 in the placebo arm (P less than .001). Overall clinical fracture was 36% lower in the romosozumab group at 12 months (P = .008). Nonvertebral fractures occurred in 56 patients (1.6%) in the romosozumab group and in 75 (2.1%) in the placebo group, a difference that did not reach statistical significance, the investigators reported Sept. 18 in the New England Journal of Medicine ( doi: 10.1056/NEJMoa1607948 ).
After 12 months, the study converted to open label with all patients receiving follow-on treatment with denosumab (Prolia), a monoclonal antibody licensed for use in osteoporosis. Patients who had received both agents in succession saw a 75% reduction of new vertebral fractures at 24 months, compared with those who had received placebo and then denosumab (fracture incidence 0.6% vs. 2.5%; P less than .001). In a subgroup of patients selected for analysis (n = 128), romosozumab substantially increased bone mineral density.
After 12 months of treatment, the percentage change from baseline was significantly greater with romosozumab than with placebo, ranging from 13.3 percentage points at the lumbar spine to 5.9 at the femoral neck (P less than .001). The gains were maintained or continued to increase after the second-year switch to denosumab. Dr. Cosman and her colleagues wrote in their analysis that the rate of nonvertebral fracture in the placebo group was two-thirds lower than expected in one of the major regions of the study (Latin America), and that this might help explain the lower-than-expected difference in nonvertebral fracture outcomes at 12 months.
Nearly all study authors, including the lead author, received grant support from Amgen or UCB Pharma, the study’s sponsors. Seven authors were employees of either Amgen or UCB, and others disclosed additional financial relationships.
