DENVER – in an extended analysis of the FRAME study.
The combination had already proven effective at 12 months and 24 months (N Engl J Med. 2016 Oct 20;375[16]:1532-43).
Romosozumab binds sclerostin, leading to both increased bone formation and decreased bone resorption, though its activity favors formation, leading it to be classified as an anabolic agent. Denosumab is an antibody that targets receptor-activated nuclear factor–kappaB ligand (RANKL), interfering with osteoclast formation and the accompanied breakdown of bone.
Dr. E. Michael Lewiecki
In the FRAME study, women aged 55-90 years with a T score of –2.5 or less in the total hip or femoral neck received romosozumab or placebo for 12 months, and then all patients were switched to denosumab at 12 months to 24 months. At 24 months, women who initially received romosozumab had a 75% relative risk reduction in new vertebral fractures and a 33% reduction in clinical fractures, compared with those who began with placebo, Dr. Lewiecki said at the annual meeting of the American Society for Bone and Mineral Research.
Of 7,180 women initially enrolled, 5,743 (80%) completed the study out to 36 months, when women who initially received 12 months of romosozumab had lower rates of new vertebral fractures than did the placebo group (1.0% vs. 2.8%; P less than .001), clinical fractures (4.0% vs. 5.5%; P = .004), and nonvertebral fractures (3.9% vs. 4.9%; P = .039).
Bone mineral density also continued to improve at month 36, with an increase of 18.1% in the lumbar spine and 9.4% in the total hip in the romosozumab group, compared with 7.5% and 4.2%, respectively, in the group that initially received placebo.
Both the placebo and romosozumab groups had similar rates of adverse events. At month 24, there were two cases of osteonecrosis of the jaw and one case of atypical femoral fracture. No new cases of either condition were observed in months 24-36.
Notably, there was no difference in risk for cardiovascular disease, with rates of 3.6% in the romosozumab patients and 3.5% in the placebo patients at 36 months. The development of romosozumab ran into a snag earlier this year when researchers found an increased risk of cardiovascular disease in the romosozumab arm of the ARCH study, in which patients received either romosozumab or alendronate for the first 12 months and then switched to alendronate (N Engl J Med. 2017 Sep 11. doi: 10.1056/NEJMoa1708322). At the end of the first year, patients in the romosozumab group had a higher rate of cardiovascular events (2.5% vs. 1.9%). That finding led the Food and Drug Administration to reject the application. Amgen and UCB are refiling in hopes of a 2018 approval.
As to romosozumab’s place in a treatment landscape that already includes teriparatide and abaloparatide, Dr. Lewiecki said, “I think it will depend on the product label. It’s not a self-administered subcutaneous injection like teriparatide and abaloparatide: The patient would present to a doctor’s office once a month for a year to get an injection – and that may be preferable to some patients,” he said.
The study was sponsored by Amgen and UCB. Dr. Lewiecki has consulted for Amgen.