Phase III BRIDGE trial of AMG 785 (romosozumab) in osteporosis meets primary endpoints- Amgen/UCB

Amgen and UCB announced positive top-line results for AMG 785 (romosozumab) from the pivotal Phase III BRIDGE trial assessing the efficacy and safety of romosozumab in treating men with osteoporosis. These data showed the BRIDGE study met the primary endpoint, demonstrating a statistically significant increase in bone mineral density (BMD) at the lumbar spine (as assessed by dual energy x-ray absorptiometry) in men with osteoporosis treated with romosozumab compared with placebo at 12 months. All secondary endpoints comparing romosozumab with placebo were also met.

Patients receiving romosozumab experienced a statistically significant increase in BMD at the femoral neck and total hip at 12 months and a statistically significant increase in BMD at the lumbar spine, femoral neck, and total hip at six months, compared with those receiving placebo. The overall patient incidence of adverse events and serious adverse events (SAEs) was generally balanced between arms. 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 (CV) SAEs 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.

Amgen and UCB recently reported the results of the FRAME study in 7,180 postmenopausal women with osteoporosis in which the overall patient incidences of adjudicated CV SAEs were balanced. Further analysis of the Phase III BRIDGE study data is ongoing and will be submitted to a future medical conference and for publication. UCB and Amgen plan to discuss these results with global regulators.

Comment: A further entrant to this market is abaloparatide from Radius Health. This synthetic peptide analog of human parathyroid hormone related protein (hPTHrP) - a bone builder - was filed in the EU in late 2015. Abaloparatide reduced major osteoporotic fractures by 67% compared to placebo and by 53% compared to Forteo in the ACTIVE trial. It also showed statistically significant reductions in both vertebral and non vertebral fractures. Abaloparatide achieved an even higher 86% reduction in spine fracture risk compared with a placebo, but is a daily injectable while Amgen's drug is injected once a month.