UCB And Amgen Announce Positive Topline Results From The Phase 3 Study Of Romosozumab in Postmenopausal Women With Osteoporosis
- FRAME Study Met All Primary Endpoints by Reducing the Incidence of New Vertebral Fracture Through 12 and 24 Months
Brussels, Belgium, Thousand Oaks, Calif, 22 February 2016 – 07:00am (CET) -regulated information - UCB (Euronext Brussels: UCB) and Amgen (NASDAQ:AMGN) today announced top-line results from the Phase 3 placebo-controlled FRActure study in postmenopausal woMen with ostEoporosis (FRAME). These data showed FRAME met the co-primary endpoints by reducing the incidence of new vertebral fracture through months 12 and 24 in postmenopausal women with osteoporosis treated with romosozumab.
The study also met the secondary endpoint of reducing the incidence of clinical fractures (composite of vertebral and non-vertebral fractures) in postmenopausal women with osteoporosis through 12 months. However, the secondary endpoint of reducing the incidence of non-vertebral fractures through months 12 and 24 was not met.
“These data are encouraging and in meeting the co-primary endpoints of this study, romosozumab has shown to be effective in reducing the incidence of new vertebral fractures at months 12 and 24 and for clinical fractures as early as 12 months,” said Professor Dr. Iris Loew-Friedrich, Chief Medical Officer and Executive Vice President, UCB. “Deeper understanding of the results will help us sharpen the profile of romosozumab in postmenopausal women with osteoporosis."
Results from the FRAME study showed that women receiving subcutaneous injection of romosozumab monthly experienced a statistically significant 73 percent reduction in the relative risk of a vertebral (spine) fracture through 12 months compared to those receiving placebo. The effect size persisted after both groups were transitioned to denosumab through the second year of treatment. Specifically, through month 24, romosozumab followed by denosumab reduced the relative risk of new vertebral fractures by a statistically significant 75 percent compared to placebo followed by denosumab. Additionally, patients receiving romosozumab experienced a statistically significant 36 percent reduction in the relative risk of a clinical fracture through 12 months compared to those receiving placebo.
“A vertebral fracture due to osteoporosis can be a life-altering event and the risk of these kinds of fractures will be a growing burden as our society ages,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “These data show that romosozumab reduced new vertebral fracture risk as soon as 12 months."
The percentage of patients with adverse events and serious adverse events in the 12-month double-blind period and 24-month study period were balanced overall between the treatment groups. In the initial 12-month treatment period, the most commonly reported adverse events in both arms (greater than 10 percent) were arthralgia, nasopharyngitis and back pain. Injection site reactions were reported in 5.2 percent of patients in the romosozumab treatment group and 2.9 percent in the placebo group during the 12-month period. Most injection site reactions were reported as mild in severity. Sub-studies evaluating hearing loss and worsening of knee osteoarthritis showed no difference between the treatment groups. There were two positively adjudicated events of osteonecrosis of the jaw in the romosozumab treatment group, one after completing romosozumab dosing and the other after completing romosozumab treatment and receiving the initial dose of denosumab. There was one positively adjudicated event of atypical femoral fracture after three months of romosozumab treatment.
FRAME is a Phase 3 multi-center, international, randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of romosozumab treatment in postmenopausal women with osteoporosis. The study evaluated 12 months of romosozumab treatment versus placebo followed by 12 months of open-label denosumab treatment for both arms. The purpose of this study was to determine if treatment with romosozumab is effective in reducing the risk of fracture in women with postmenopausal osteoporosis through months 12 and 24.
Further analysis of the Phase 3 FRAME 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 in anticipation of a potential filing in 2016.
Romosozumab is an investigational bone-forming monoclonal antibody and is not approved by any regulatory authority for the treatment of osteoporosis. It is designed to work by inhibiting the protein sclerostin, and has a dual effect on bone, both increasing bone formation and decreasing bone resorption.1,2,3 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.
About the FRAME study
FRAME is a multi-center, international, randomized, double-blind, placebo-controlled, parallel-group study in postmenopausal women with osteoporosis, defined as low bone mineral density at the total hip or femoral neck. The study evaluated the effectiveness of romosozumab treatment, compared with placebo, in reducing the risk of new vertebral fractures through 12 months. The study also further evaluated if romosozumab treatment for 12 months followed by denosumab treatment for 12 months, compared with placebo followed by denosumab treatment, was effective in reducing the risk of new vertebral fractures through 24 months. In addition, clinical fracture (a composite endpoint of symptomatic vertebral and non-vertebral fractures) risk reduction, non-vertebral fracture (fractures outside of the spine, excluding sites that are not considered osteoporotic, fractures due to high trauma or pathologic fractures) risk reduction and other endpoints were assessed at 12 and 24 months.
7,180 patients were randomized 1:1 to receive either 210 mg romosozumab subcutaneous (SC) monthly (QM) or placebo SC QM for the 12-month double-blind study period. After the placebo-controlled study period, patients entered the open-label phase where all patients received 60 mg denosumab SC every six months (Q6M) for 12 months, while remaining blinded to initial treatment. An additional 12 month extension period of open-label 60 mg denosumab SC Q6M is currently ongoing.
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 8500 people in approximately 40 countries, the company generated revenue of € 3.3 billion in 2014. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news.
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- Padhi D, et al. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011;36(1):19-26.
- Li X, et al. Sclerostin antibody treatment increases bone formation, bone mass and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009;24:578-588.
- Ominsky MS, et al. Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of non-fractured bones. J Bone Miner Res. 2011;26:1012-1021.
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