Clinical Trials

Date: 2015-10-12

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting

Company: Amgen (USA - CA) UCB (Belgium)

Product: romosozumab (CDP7851/AMG 785)

Action mechanism: monoclonal antibody. Romosozumab is an investigational bone-forming agent that is designed to work by inhibiting the protein sclerostin, thereby increasing bone formation and decreasing bone breakdown.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 patients with osteoporosis. Romosozumab is being co-developed by Amgen and UCB.

Disease: postmenopausal women with low bone mineral density

Therapeutic area: Bone diseases - Women's health

Country:

Trial details:

Latest news: * On October 12, 2015, Amgen and UCB  presented additional findings from an exploratory sub-study of the previously reported romosozumab Phase 2 trial. The findings were presented in an oral plenary session at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting in Seattle . The small exploratory sub-study data showed that, at month 12, the investigational bone-forming agent romosozumab increased estimated bone strength (percent change from baseline) at the spine and hip more than open-label teriparatide in postmenopausal women with low bone mass. These results were measured by a validated method called finite element analysis (FEA), which utilized quantitative computed tomography (QCT) scans to simulate compression overload to estimate vertebral strength, and a sideways fall to estimate femoral strength.2 The FEA showed that, at the spine, women in the romosozumab group (210 mg once monthly, n=24) increased estimated strength compared to baseline by 27.3 percent at month 12, which was greater than placebo (-3.9 percent, n=27) and teriparatide (18.5 percent, n=28).2 At the hip, the estimated strength increased from baseline by 3.6 percent with romosozumab (n=9), compared with placebo (-0.1 percent, n=18) or teriparatide (-0.7 percent, n=19).2 These data are from a small exploratory sub-study (n=79) of a Phase 2 trial (NCT00896532) that included a total of 419 patients. A subset of these women underwent spine and hip QCT imaging to measure bone mineral density (BMD) gains.3 To investigate the effects of romosozumab on bone strength an FEA was performed on these QCT scans. Adverse events in the original Phase 2 study were similar across groups, except for mild, generally non-recurring injection site reactions observed more frequently with romosozumab compared to placebo, but with no observed dose-related relationship. The most common adverse events included mild upper respiratory tract infection, pain in the back and joints, and headache. These reactions did not lead to study drug discontinuation or study withdrawal; the safety of romosozumab will be further addressed in subsequent larger studies. * On September 15, 2014, Amgen and UCB announced results from several exploratory analyses of the Phase 2 study evaluating romosozumab in postmenopausal women with low bone mineral density (BMD).  These data were presented at the American Society for Bone and Mineral Research (ASBMR) 2014 Annual Meeting in Houston, Sept. 12-15, 2014. Results from one analysis showed that treatment with romosozumab led to significant increases in lumbar spine and total hip BMD during the first 12 months, with continued increases through year two. After year two, patients transitioned to either treatment with Prolia® (denosumab) for 12 months, which led to further BMD increases, or to placebo, in which case BMD decreased towards initial baseline. An additional analysis of the Phase 2 study found that women treated with romosozumab had greater improvements in cortical parameters of the vertebrae, including thickness and mass, compared with those taking open-label Forteo® (teriparatide) or placebo at 12 months. In the Phase 2 study, after 12 months of treatment with romosozumab adverse events were similar across groups, except for mild, generally non-recurring injection site reactions observed more frequently with romosozumab compared with placebo, but with no observed dose-related relationship. These reactions did not lead to study drug discontinuation or study withdrawal. The most frequent adverse events included nasopharyngitis and arthralgia. The romosozumab adverse event profile in year two was comparable to year one of the study. The overall proportions of subjects reporting adverse events and serious adverse events in the 24 month period were balanced across treatment groups. In year three of the study, the overall subject incidence of adverse events and serious adverse events were balanced across treatment groups. No new safety findings were observed. "Effects of 2 Years of Treatment with Romosozumab Followed by One Year of Denosumab or Placebo in Postmenopausal Women with Low BMD" Results: • In this exploratory analysis, romosozumab led to increases in lumbar spine and total hip BMD during year one with continued increases through year two. The largest gains in BMD were observed with the 210 mg monthly dose, achieving an increase of 15.7 percent (lumbar spine BMD) and 6.0 percent (total hip BMD). Women receiving romosozumab 210 mg monthly who then transitioned to treatment with Prolia after 12 months continued to accrue BMD at a rate similar to what was seen during the second year of treatment with romosozumab; in those who transitioned to placebo, BMD returned towards pre-treatment levels. Methods: • The study enrolled 419 postmenopausal women aged 55 to 85 years with a lumbar spine, total hip or femoral neck T score ?-2.0 and ?-3.5. Women received one of five regimens of romosozumab (70 mg monthly, 140 mg monthly, 210 mg monthly, 140 mg once every three months, 210 mg once every three months), or placebo for two years. At the end of two years, eligible subjects entered a one year double blind extension phase and were re-randomized 1:1 within their original treatment group to placebo or denosumab 60 mg once every six months. Only women who entered the extension were included in this analysis (n=260). "Romosozumab and Teriparatide Effects on Vertebral Cortical Mass, Thickness and Density in Postmenopausal Women with Low BMD" Results: • In this exploratory analysis, results showed that treatment with romosozumab resulted in a mean (95 percent CI) cortical thickness (CTh) increase of 11.2 percent (9.0 to 13.4), a cortical bone mineral density (CBMD) increase of 1.6 percent (0.2 to 2.9), a cortical mass (CMass) increase of 12.7 percent (10.8 to 14.7) and a trabecular BMD (TBMD) increase of 22.2 percent (19.2 to 25.3). The improvements in CTh (p<0.001) and CMass (p<0.001) with romosozumab were significantly greater than those observed with open-label teriparatide. • Treatment with teriparatide resulted in a CTh increase of 5.6 percent (3.9 to 7.4), a CMass increase of 4.6 percent (3.4 to 5.8), a TBMD increase of 17.4 percent (12.2 to 22.6), and a slight but not significant CBMD reduction of 0.5 percent (–1.8 to 0.7). • In the placebo group, the statistically significant change was a reduction of 4.3 percent (–6.7 to –1.9) in TBMD. Methods: • Baseline and 12 month L1 vertebral computed tomography (CT) scans from postmenopausal women treated with romosozumab (210 mg monthly, n=17), teriparatide (20 µg daily, n=19) and placebo (n=20) were evaluated. • Cortical measurements were performed, blinded to treatment, using the Stradwin software tool, which is able to measure and map CBMD, TBMD directly adjacent to the cortex, CTh and CMass (CMass=0.1 × CTh × CBMD). • Transferring these maps to a canonical vertebral surface allows evaluation and topographical illustration of longitudinal changes to determine differences between treatments. Amgen and UCB have announced that they look forward to reporting the results of the romosozumab Phase 3 program in 2016.

Is general: Yes