Amgen and UCB have reported the findings from the FRAME study indicating that the investigational agent romosozumab significantly reduced the incidence of new vertebral fractures in postmenopausal women with osteoporosis during a 12 and 24 month period, thereby meeting the study’s co-primary endpoints.
The Phase 3 trial is the first to evaluate fracture risk reduction as early as one year for its primary endpoint.
Romosozumab binds and inhibits the activity of the protein sclerostin and therefore has a dual effect on bone, increasing bone formation and decreasing bone breakdown.
Fracture study in postmenopausal women with osteoporosis (FRAME) witnessed the enrolment of 7,180 women.
The study demonstrated that those randomly assigned to receive a monthly subcutaneous 210mg dose of romosozumab experienced a statistically significant 73% reduction in the relative risk of a new vertebral (spine) fracture over 12 months, which is the first co-primary endpoint, compared to those receiving placebo (fracture incidence 0.5% versus 1.8%, respectively).
The data also indicated that by six months, new vertebral fractures occurred in 14 romosozumab and 26 placebo patients, and between six and 12 months, fractures occurred in two additional romosozumab patients compared to 33 additional placebo patients.
For patients who received romosozumab in year one, fracture risk reduction continued throughout month 24 after both groups transitioned to denosumab treatment in the second year of the study.
There was a statistically significant 75% reduction in the risk of vertebral fracture at month 24 in patients who received romosozumab followed by denosumab, compared with placebo followed by denosumab (fracture incidence 0.6% versus 2.5% respectively).
The second year of the study found that new vertebral fractures occurred in five patients who transitioned from romosozumab to denosumab and 25 patients who transitioned from placebo to denosumab.
On observing clinical fractures, which encompass all symptomatic fractures including non-vertebral and painful vertebral, patients receiving romosozumab experienced a statistically significant 36% reduction in the relative risk of a clinical fracture, a secondary endpoint, through 12 months compared to those receiving placebo (fracture incidence 1.6% versus 2.5%, respectively).
The study also saw a 33% reduction in relative risk of clinical fracture through 24 months after patients transitioned from romosozumab to denosumab, compared to patients transitioning from placebo to denosumab.
Romosozumab led to a 25% reduction compared to placebo in the relative risk of non-vertebral fractures through month 12, another secondary endpoint, though the reduced risk was not statistically significant (fracture incidence 1.6% versus 2.1%, respectively).
For the non-vertebral fracture endpoint, the total fracture incidence in the study was lower than expected (2.1% in the placebo group in year one versus an expected rate of 3.5%).
Amgen research and development executive vice president Sean E. Harper said: “We are pleased to see nearly 15 years of sclerostin antibody research reinforced with this 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.
“These positive FRAME study results are the basis of our Biologics Licensing Application 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.”