Date: 2016-02-22
Type of
information: Publication of results in a medical journal
phase: 3a
Announcement: publication of results in The New English Journal of Medicine
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.
- 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.
Disease: postmenopausal women with osteoporosis
Therapeutic
area: Bone diseases
Country:
Trial
details:
- FRAME ( FRActure study in postmenopausal woMen with ostEoporosis) 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.
Latest
news:
- • On September 18, 2016, Amgen and UCB announced findings from the FRAME study showing that 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 were published in the New England Journal of Medicine (NEJM) and presented in an oral session at the Annual Meeting of the American Society for Bone Mineral Research (ASBMR) in Atlanta .
FRAME ,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 fracture through 12 months, the first co-primary endpoint, compared to those receiving placebo (fracture incidence 0.5 percent versus 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 patients.
- 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 versus placebo followed by denosumab (fracture incidence 0.6 percent versus 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.
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 versus 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 versus 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 sub-study 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 (p<0.001 compared to placebo-to-denosumab group for all comparisons).
- • On February 22, 2016, Amgen and UCB announced top-line results from the Phase 3 placebo-controlled(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.
- 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 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 fracture 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.
- 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. Substudies 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.
- 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.
Is
general: Yes
