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FRAME Data Simultaneously Published in New England Journal of Medicine and Presented at ASBMR Showed Treatment With Romosozumab Significantly Reduced New Vertebral and Clinical Fractures Through 12 Months
Significant Bone Mineral Density Gains Shown at Six and 12 Months at the Lumbar Spine, Total Hip and Femoral Neck
Bone Mineral Density Continued to Increase and Vertebral Fracture Risk Reduction Persisted With the Transition From Romosozumab to Denosumab Through 24 Months
THOUSAND OAKS, Calif. and BRUSSELS (Sept. 18, 2016) - Amgen (NASDAQ:AMGN) and UCB (Euronext Brussels: UCB) today announced findings from the FRAME study showing that investigational agent romosozumab significantly reduced the incidence of new vertebral fractures in postmenopausal women with osteoporosis through 12 and 24 months, meeting the study’s co-primary endpoints. The results from the Phase 3 study, the first to evaluate fracture risk reduction as early as one year as a primary endpoint, were published in the New England Journal of Medicine (NEJM), and presented today in an oral session at the American Society for Bone Mineral Research (ASBMR) annual meeting in Atlanta. Romosozumab works by binding and inhibiting the activity of the protein sclerostin, and as a result has a dual effect on bone, both increasing bone formation and decreasing bone breakdown.
“Treatment data show that only one in five women who have experienced an osteoporotic fracture are started on treatment for the disease1, despite the fact that patients who experience an osteoporotic fracture are twice as likely to suffer a future fracture2,” said study lead author Felicia Cosman, M.D., medical director of the Clinical Research Center at Helen Hayes Hospital and professor of medicine at Columbia University College of Physicians and Surgeons in New York. “The FRAME results demonstrate that romosozumab, with its dual effect of increasing bone formation and decreasing bone resorption, has the potential to reduce the risk of new vertebral and clinical fractures within 12 months, in addition to showing improvements in bone mass, with sustained benefits upon transition to denosumab, thereby addressing a critical treatment need for patients at increased risk of fracture.”
FRAME (FRActure study in postmenopausal woMen with ostEoporosis), which enrolled 7,180 women, showed that those randomly assigned to receive a monthly subcutaneous 210 mg dose of romosozumab experienced a statistically significant 73 percent reduction in the relative risk of a new vertebral (spine) fracture through 12 months, the first co-primary endpoint, compared to those receiving placebo (fracture incidence 0.5 percent vs. 1.8 percent, respectively [p<0.001]). of="" interest,="" the="" data="" showed="" that="" by="" six="" months,="" new="" vertebral="" fractures="" occurred="" in="" 14="" romosozumab="" and="" 26="" placebo="" patients,="" and="" between="" six="" to="" 12="" months,="" fractures="" occurred="" in="" two="" additional="" romosozumab="" patients="" versus="" 33="" additional="" placebo="">0.001]).>
For those patients who received romosozumab in year one, fracture risk reduction persisted through month 24 after both groups transitioned to denosumab treatment in the second year of the study; there was a statistically significant 75 percent reduction in the risk of vertebral fracture at month 24 (the other co-primary endpoint) in patients who received romosozumab followed by denosumab vs. placebo followed by denosumab (fracture incidence 0.6 percent vs. 2.5 percent, respectively [p<0.001]). in="" the="" second="" year="" of="" the="" study,="" new="" vertebral="" fractures="" occurred="" in="" five="" patients="" who="" transitioned="" from="" romosozumab="" to="" denosumab="" and="" 25="" patients="" who="" transitioned="" from="" placebo="" to="" denosumab.="">0.001]).>
When looking at clinical fractures, which encompass all symptomatic fractures (both non-vertebral and painful vertebral fractures), patients receiving romosozumab experienced a statistically significant 36 percent reduction in the relative risk of a clinical fracture, a secondary endpoint, through 12 months compared to those receiving placebo (fracture incidence 1.6 percent vs. 2.5 percent, respectively [p=0.008]). A 33 percent reduction in relative risk of clinical fracture was observed through 24 months after patients transitioned from romosozumab to denosumab compared to patients transitioning from placebo to denosumab (nominal p=0.002, adjusted p=0.096).
Romosozumab resulted in a 25 percent reduction compared to placebo in the relative risk of non-vertebral fractures through month 12, another secondary endpoint, but the reduced risk was not statistically significant (fracture incidence 1.6 percent vs. 2.1 percent, respectively, [p=0.096]. For the non-vertebral fracture endpoint, the overall fracture incidence in the study was lower than expected (2.1 percent in the placebo group in year one versus an expected rate of 3.5 percent).
In a substudy of 126 subjects, romosozumab increased bone mineral density with gains of 9.7 percent and 4.7 percent from baseline by six months at the lumbar spine and total hip, respectively, and gains of 13.3 percent and 6.8 percent at 12 months (all comparisons versus placebo p<0.001). bone="" mineral="" density="" continued="" to="" increase="" in="" the="" romosozumab="" group="" after="" transitioning="" to="" denosumab,="" reaching="" 17.6="" percent="" and="" 8.8="" percent="" increases="" from="" baseline="" at="" the="" lumbar="" spine="" and="" total="" hip,="" respectively,="" at="" 24="" months="">0.001).><0.001 compared="" to="" placebo-to-denosumab="" group="" for="" all="" comparisons).="">0.001>
“We are pleased to see nearly 15 years of sclerostin antibody research reinforced with these Phase 3 data. Romosozumab with its dual effect as a bone builder and anti-resorptive has the potential to play a distinct and important role in the treatment of women with postmenopausal osteoporosis at increased risk of fracture,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “These positive FRAME study results are the basis of our Biologics Licensing Agreement that we submitted to the FDA in July, and we look forward to working with regulatory authorities to help make this potential treatment option available to patients.”
“Osteoporotic fractures are common, resulting in far-reaching consequences for individuals and their families, as well as for society as a whole,” said Dr. Pascale Richetta, head of bone and executive vice president, UCB. “To reduce the growing global burden of this prevalent chronic disease, more decisive steps need to be taken now for identifying, diagnosing and appropriately treating people with osteoporosis at an increased risk of fracture.”
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. Injection site reactions, mostly mild in severity, 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. 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. Adjudicated serious cardiovascular events and cardiovascular deaths were balanced between treatment groups.
About RomosozumabRomosozumab is an investigational bone-forming monoclonal agent and is not approved by any regulatory authority for the treatment of osteoporosis. It is designed to work by inhibiting the activity of the protein sclerostin and has a dual effect on bone, both 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 postmenopausal women with osteoporosis. Amgen and UCB are co-developing romosozumab.
About the FRAME studyFRAME 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 which encompasses all symptomatic fractures, both non-vertebral and painful 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.
About the Amgen and UCB CollaborationSince 2004, Amgen and UCB have been working together under a collaboration and license agreement to research, develop and market antibody products targeting the protein sclerostin. As part of this agreement, the two companies continue to collaborate on the development of romosozumab for the treatment of osteoporosis. This gene-to-drug project demonstrates how Amgen and UCB are joining forces to turn genetic discoveries into new medicine, turning conceptual science into a reality.
About AmgenAmgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
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