Amgen and UCB announced results from the phase 3 BRIDGE study showing that in men with osteoporosis, the investigational agent romosozumab resulted in significant bone mineral density (BMD) gains at the lumbar spine, total hip and femoral neck compared to placebo at six and 12 months. The full findings are being presented for the first time at the American College of Rheumatology (ACR) and Association of Rheumatology Health Professionals (ARHP) Annual Meeting in Washington, D.C., November 11-16, 2016.
Although more common in women, osteoporosis is also a serious health issue for men. One in five men over the age of 50 worldwide will have an osteoporosis-related fracture - an incidence that is greater than the development of prostate cancer. Men are less likely to be diagnosed with osteoporosis and treated, while fractures can be associated with increased rates of disability compared to women.
"Romosozumab has the ability to improve bone mass, structure and strength by both increasing bone formation and decreasing bone resorption," said E. Michael Lewiecki, M.D., principal investigator for the BRIDGE study and clinical assistant professor of medicine, University of New Mexico School of Medicine, Albuquerque, N.M. "These phase 3 findings are particularly promising as they show the clinical effects of romosozumab in men with osteoporosis - a population that is often under-recognized and under-treated for a disease that can have devastating consequences."
The BRIDGE study (placeBo-contRolled study evaluatIng the efficacy anD safety of romosozumab in treatinG mEn with osteoporosis) involved 245 men with osteoporosis (163 romosozumab, 82 placebo) randomized 2:1 to receive either 210 mg romosozumab or placebo subcutaneously once monthly for 12 months. All patients received daily calcium and vitamin D. The primary endpoint was met, with romosozumab demonstrating a statistically significant increase (12.1 percent; p<0.01) in BMD at the lumbar spine (as assessed by dual energy x-ray absorptiometry) compared with placebo at 12 months. All secondary endpoints were also met with romosozumab showing a statistically significant increase in BMD at total hip (2.5 percent) and the femoral neck (2.2 percent) at 12 months (both p<0.01 compared to placebo). A statistically significant increase in BMD at six months was also seen with romosozumab at all sites examined compared to placebo: lumbar spine (9.0 percent), total hip (1.6 percent), femoral neck (1.2 percent; p<0.01 for all sites). The dual effect of romosozumab was reflected by an increase in P1NP (86 percent median increase from baseline peaking at one month), a marker of bone formation, and a decrease in CTX (31 percent median decrease from baseline at one month), a marker of bone resorption.
The overall incidence of adverse events and serious adverse events were balanced between treatment groups. The most frequently reported adverse events (greater than five percent in the romosozumab arm) were nasopharyngitis, back pain, hypertension, headache and constipation. Injection site reactions were reported in 5.5 percent of patients in the romosozumab treatment group and 3.7 percent in the placebo group during the 12-month period. Most injection site reactions were reported as mild in severity. The patient incidence of positively adjudicated cardiovascular serious adverse events was 4.9 percent (8/163) in the romosozumab group and 2.5 percent (2/81) in the placebo group. The patient incidence of positively adjudicated cardiovascular death was 0.6 percent (1/163) in the romosozumab group and 1.2 percent (1/81) in the placebo group.
The BRIDGE study is part of the comprehensive phase 3 program for romosozumab and complements positive results from two additional studies at the ACR/ARHP Annual Meeting focusing on romosozumab in postmenopausal women with osteoporosis - the FRAME study and the STRUCTURE study.
BRIDGE is a multicenter, international, randomized, double-blind, placebo-controlled study in men aged 55-90 years with a lumbar spine, total hip or femoral neck BMD T score = -2.5 or = -1.5 and a history of fragility non-vertebral fracture (excluding hip fracture) or vertebral fracture. The study evaluated the effectiveness of romosozumab treatment for 12 months, compared with placebo, in increasing BMD at the lumbar spine, as well as the effect on BMD at the femoral neck and total hip at 12 months and at six months, and the percent change from baseline in the serum bone turnover markers P1NP and CTX.
Romosozumab is an investigational bone-forming monoclonal agent and is not approved by any regulatory authority for the treatment of osteoporosis. It is designed to work by inhibiting the activity of the protein sclerostin and has a dual effect on bone, increasing bone formation and decreasing bone resorption. Romosozumab is being studied for its potential to reduce the risk of fractures in an extensive global phase 3 program. This program includes two large fracture trials comparing romosozumab to either placebo or active comparator in more than 10,000 postmenopausal women with osteoporosis. Amgen and UCB are co-developing romosozumab. In September 2016, Amgen and UCB announced that the US Food and Drug Administration (FDA) accepted for review the Biologics License Application (BLA) for romosozumab for the treatment of osteoporosis in postmenopausal women at increased risk of fracture.
Since 2004, Amgen and UCB have been working together under a collaboration and license agreement to research, develop and market antibody products targeting the protein sclerostin. As part of this agreement, the two companies continue to collaborate on the development of romosozumab for the treatment of osteoporosis. This gene-to-drug project demonstrates how Amgen and UCB are joining forces to translate a genetic discovery into a new medicine, turning conceptual science into a reality.