Romosozumab Continues to Build Bone, Reduce Fracture Risk

Romosozumab has been shown to reduce the risk of clinical vertebral fractures in postmenopausal women with osteoporosis by as much as five times as compared to a placebo group.

The study, presented on June 14 at the 2017 European Congress of Rheumatology (EULAR) meeting in Madrid, showed that over the course of 12 months, women in the treatment group experienced rapid and large reductions in their risk of a vertebral fracture as compared to the placebo group.

“In this talk today, I centered on the one year affect not only on radiographic vertebral fractures, but on clinical fractures in which there was a significant reduction of more than 80% within one year compared to placebo,” said Dr. Piet Geusens, of Maastricht University (Netherlands), in a video interview. [[{"type":"media","view_mode":"media_crop","fid":"60719","attributes":{"alt":"Dr. Piet Geusens, Maastricht University, The Netherlands","class":"media-image media-image-right","id":"media_crop_7946967147566","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7676","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; float: right;","title":"Dr. Piet Geusens, Maastricht University, The Netherlands","typeof":"foaf:Image"}}]]

Romosozumab (Amgen/UCB) is an investigational monoclonal antibody currently under review by the FDA for the treatment of osteoporosis in postmenopausal women who are at increased risk of fracture.

By binding and inhibiting sclerostin, a protein present in bone, romosozumab increases bone formation while decreasing resorption which leads to increased bone mineral density (BMD) as shown in this study. At six months, increases in BMD were identified in the trabecular and cortical sections of the spine, which led to significant reductions in the risk of vertebral fractures.

The data from this study is based on the Fracture Study in Postmenopausal Women with Osteoporosis (FRAME), a phase three randomized, double-blind clinical trial of 7,180 postmenopausal women who received monthly doses of romosozumab (n=3,589; 210 mg) or a placebo (n=3,591) for 12 months.

The new analysis presented at EULAR focused on the incidence of clinical vertebral fractures in women with back pain. Of 119 women with back pain lasting longer than 12 months, 20 were diagnosed with a new or worsening vertebral fracture. There were three clinical vertebral fractures (<0.1% of patients all occurring in the first two months) in the romosozumab treatment group as compared to 17 clinical fractures (0.5%) in the placebo group. At 12 months, the incidence of clinical vertebral fracture risk was 83% lower in the treatment group. In women with clinical vertebral fractures, bone mineral density measures showed more severe osteoporosis.

In women with clinical vertebral fracture, the lumbar spine T-score was lower as compared to the non-fracture group and the FRAX score was higher at baseline.

“We don’t have direct comparisons between romosozumab and other bone-forming drugs currently available, however, if you look at the quick and rapid effects on clinical vertebral fractures within one year of treatment, we had only three patients who had vertebral fractures within two months. It reduced the risk of vertebral fractures very rapidly and the same was true of clinical fractures,” Dr. Geusens said.

Related studies

A 2016 study published in the journal Calcified Tissue International showed that monthly doses of subcutaneous romosozumab, administered over the course of one year, led to gains in both trabecular and cortical compartments bone in the spine and hip regions.

A report published in theNew England Journal of Medicinelast year showed similar results. The data, which was also based on the FRAME study, showed that after 12 months of romosozumab treatment, only 0.5% (16 of 3,321) of treated patients had new vertebral fractures as compared to 1.8% (59 of 3,322) in the placebo group, which equates to a 73% lower risk of fracture with romosozumab (P<0.001). Clinical fractures occurred in 1.6% (58 of 3,589) of treated patients as compared to 2.5% (90 of 3,591) in the placebo group, which equates to a 36% lower risk of fracture. (P=0.008).

Disclosures:

This study was funded by by Amgen Inc. and UCB Pharma.

References:

Geusens P, Oates M, Miyauchi A, et al. Romosozumab rapidly reduces clinical vertebral fracture incidence: results from the FRAME study. EULAR 2017; Madrid: Abstract OP0048

Appelman-Dijkstra NM, Papapoulos SE. Sclerostin Inhibition in the Management of Osteoporosis. Calcified Tissue International. 2016; 98: 370-380

Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med 2016; 375: 1532-1543.