优时比/安进单抗药物Romosozumab临床II期效果显著

优时比/安进单抗药物Romosozumab临床II期效果显著

                               
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发布日期：2014-09-17  来源：streetinsider  
优时比制药和安进 9月16日 联合宣布，公司单抗药物Romosozumab在临床II期研究中表现良好。该药物适应对象为低骨密度的绝经期后妇女。

　　

                               
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　　Romosozumab是一种实验性完全人源化单抗药物，通过抑制蛋白质硬化素从而促进骨形成和减少骨质破损。

　　根据公司发布的临床II期结果显示，患者在接受romosozumab一年的治疗之后，腰椎骨和髋骨的骨密度出现大幅度上升，并在之后一年内继续上升。

　　Romosozumab目前正在进行安慰剂对照的临床III期研究，目标是观测该药物是否能降低骨折的风险，有超过1万位骨质疏松症患者参与。

　　

Amgen (AMGN), UCB Present Data from Romosozumab Phase 2 in Postmenopausal Women with Low BMDAmgen (Nasdaq: AMGN) and UCB announced results from several exploratory analyses of the Phase 2 study evaluating romosozumab in postmenopausal women with low bone mineral density (BMD). 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. These data were presented at the American Society for Bone and Mineral Research (ASBMR) 2014 Annual Meeting in Houston, Sept. 12-15, 2014.
"Fractures or broken bones due to osteoporosis are very common and often have a life altering impact on an older woman and her family," said Michael McClung, M.D., director of the Oregon Osteoporosis Center. "It is encouraging to see that treatment with romosozumab for a second year provided additional increases in bone mineral density beyond what was seen during the first 12 months of treatment."
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.
"We are very excited about the potential of romosozumab to significantly build bone for people at high risk for fracture, in particular those who have already fractured, given the impact this can have on a patient," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We look forward to continued investigation of romosozumab in our extensive global Phase 3 program, which includes two large fracture trials comparing the treatment to either placebo or active comparators in more than 10,000 patients with osteoporosis."
Postmenopausal osteoporosis (PMO) affects many women after menopause as their ability to form new bone cannot counter the rate at which bone is being removed. This bone loss leads to weakened bones over time, increasing the potential for a broken bone or fracture.1,2 Such a break, or fracture, may be a life-changing event.2,3 about half of all women over age 50 will have an osteoporosis-related fracture in their remaining lifetime, and once that happens, the chances of another are much higher.4,5
"Despite continuing progress in the management and treatment of patients with osteoporosis, there remains a considerable need for new therapeutic approaches for individual patients," said Professor Dr. Iris Loew-Friedrich, chief medical officer and executive vice president, UCB. "Investigational studies to date suggest that the bone building capacity of romosozumab may show promise as a new treatment option to manage this serious disease. We look forward to reporting the results of the romosozumab Phase 3 program in 2016."
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.
seleced Abstracts of Interest
"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 &micro;g 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.
  

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