Date: 2016-04-01
Type of
information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at ENDO 2016, the Endocrine Society's 98th Annual Meeting & Expo in Boston
Company: Amgen (USA - CA) UCB (Belgium)
Product: romosozumab (CDP7851/AMG 785)
Action
mechanism: monoclonal antibody. Romosozumab (CDP7851/AMG 785) is a humanized monoclonal antibody that binds to and inhibits sclerostin, a protein secreted by bone cells that inhibits bone formation. By binding to and blocking sclerostin, it is designed to increase the amount of bone in the skeleton. With more than 75 million people worldwide suffering from osteoporosis, there is a serious patient need for therapeutics that help build bone.
Disease: postmenopausal osteoporosis
Therapeutic
area: Bone diseases
Country: Argentina, Belgium, Canada, Colombia, Czech Republic, Denmark, Hungary, Poland, Spain, UK, USA
Trial
details:
- The STRUCTURE study (STudy evaluating effect of RomosozUmab Compared with Teriparatide in postmenopaUsal women with osteoporosis at high risk for fracture pReviously treated with bisphosphonatE therapy) is a Phase 3, multi-center, international, randomized, open-label, teriparatide-controlled study that evaluated safety, tolerability and efficacy of romosozumab in women with postmenopausal osteoporosis.
- The trial included 436 postmenopausal women averaging 72 years of age who had postmenopausal osteoporosis and a history of bone fracture; patients were treated with bisphosphonate therapy for a minimum of three years prior to screening, with treatment with alendronate (70 mg weekly or equivalent) during the year immediately prior to screening. The women received daily calcium and vitamin D and were randomly assigned to receive either subcutaneous romosozumab 210 mg once monthly (n=218), administered by a healthcare professional, or self-administered subcutaneous teriparatide 20 mcg daily for 12 months (n=218).
- The primary endpoint was percent change from baseline in total hip BMD by DXA through month 12 (average of the changes at months six and 12). Key secondary endpoints included percent change from baseline at months six and 12 in total hip BMD by DXA; hip integral and cortical BMD by quantitative computed tomography (QCT), a method to measure BMD changes in three dimensions; and estimated hip strength by finite element analysis (FEA). FEA is a validated method that utilizes QCT scans to simulate compression overload to estimate vertebral strength, and a sideways fall to estimate femoral strength. Other secondary endpoints included lumbar spine and femoral neck BMD by DXA at months six and 12. (NCT01796301)
Latest
news:
- • On April 1, 2016, Amgen and UCB announced detailed Phase 3 results showing the investigational agent romosozumab demonstrated a statistically significant increase in hip bone mineral density (BMD) and strength compared with teriparatide in postmenopausal women with osteoporosis transitioning from bisphosphonate treatment. The data, from the STRUCTURE study were presented during an oral session at ENDO 2016. The trial included 436 women, averaging 72 years of age, with postmenopausal osteoporosis, a history of non-vertebral fracture after the age of 50, or vertebral fracture and treatment with bisphosphonate therapy for a minimum of three years prior to transitioning to romosozumab or teriparatide therapy. The women were randomly assigned to receive either subcutaneous romosozumab 210 mg once monthly (n=218) or subcutaneous teriparatide 20 mcg daily for 12 months (n=218).
- The results showed that the percent change from baseline in BMD at the total hip through month 12 (the primary endpoint, an average of the percent change from baseline at month six and 12), was significantly greater with romosozumab compared with teriparatide: 2.6 percent versus -0.6 percent, respectively (p<0.0001), for a mean difference between the two groups of 3.2 percent (p<0.0001). The measurement was based on the standard method of dual-energy x-ray absorptiometry (DXA).
- For the secondary endpoints, patients treated with romosozumab had significantly larger increases from baseline in BMD and strength compared with those taking teriparatide, with mean differences ranging from 3.1 percent to 4.6 percent (all p-values <0.0001):
| Percent change from baseline |
Romosozumab |
Teriparatide |
Mean Difference |
| Total hip BMD changes by DXA at six months |
2.3 percent |
–0.8 percent |
3.1 percent |
| Total hip BMD changes by DXA at 12 months |
2.9 percent |
–0.5 percent |
3.4 percent |
| Femoral neck BMD changes by DXA at six months |
2.1 percent |
–1.1 percent |
3.2 percent |
| Femoral neck BMD changes by DXA at 12 months |
3.2 percent |
–0.2 percent |
3.4 percent |
| Lumbar spine BMD changes by DXA at six months |
7.2 percent |
3.5 percent |
3.8 percent |
| Lumbar spine BMD changes by DXA at 12 months |
9.8 percent |
5.4 percent |
4.4 percent |
| Total hip integral BMD changes by quantitative computed tomography (QCT) at six months |
2.3 percent |
–0.8 percent |
3.1 percent |
| Total hip integral BMD changes by QCT at 12 months |
3.4 percent |
–0.2 percent |
3.6 percent |
| Total hip cortical BMD changes by QCT at six months |
0.7 percent |
–2.7 percent |
3.4 percent |
| Total hip cortical BMD changes by QCT at 12 months |
1.1 percent |
–3.6 percent |
4.6 percent |
| Total hip estimated strength by finite element analysis (FEA) at six months |
2.1 percent |
–1.0 percent |
3.1 percent |
| Total hip estimated strength by FEA at 12 months |
2.5 percent |
–0.7 percent |
3.2 percent |
- The overall incidence of adverse events was generally balanced between the two study arms. Incidence of all adverse events in patients treated with romosozumab was 75.2 percent compared to 69.2 percent with teriparatide. Serious adverse events occurred in 7.8 percent of patients treated with romosozumab compared to 10.7 percent for teriparatide. Adverse events reported in the romosozumab arm greater than or equal to 10 percent of patients were arthralgia and nasopharyngitis. Injection site reactions were reported in 7.8 percent.
- • On September 1, 2015, Amgen and UCB announced top-line results from the STRUCTURE trial. The study met the primary endpoint, demonstrating a statistically significant difference in favor of romosozumab in the percent change of total hip bone mineral density (measured by DXA) through month 12. The overall subject incidence of adverse events was generally balanced between arms. Adverse events in patients treated with romosozumab were similar to those previously reported and no new safety signals were detected. Adverse events reported in the romosozumab arm in more than five percent of patients were nasopharyngitis, arthralgia, back pain, headache and fall. Further analysis of the Phase 3 STRUCTURE study results are ongoing and will be submitted to a future medical conference and for publication.
- • On April 4, 2012, UCB and Amgen have announced the start of their sclerostin antibody (CDP7851/AMG 785) Phase 3 clinical trial program for the treatment of postmenopausal osteoporosis. Initial results from the Phase 3 program are expected by the end of 2015.
Is
general: Yes
