Romosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. Amgen found in studies of the drug that is was effective for one year but then the body seemed to escape the effect of the drug. In light of this, they planned the registration study of the drug to last for 1 year on Evenity to be followed by 1 year on Prolia. This “one, two punch” proved very potent and undoubtedly will be the preferred method of prescribing the drug. Evenity is a shot in the arm that is given once a month in the doctor’s office. It is already at the US FDA awaiting a decision, which is expected sometime in 2017.
Treatment of postmenopausal women with osteoporosis
Efficacy Study for Evenity for Treatment of Osteoporosis in Postmenopausal Women
Evenity was studied for 1 year in 7180 postmenopausal women who were on average age 70 and who had osteoporosis at the hip by DXA. 18% had a prevalent vertebral fracture on X-ray at the beginning of the study. 40% were Hispanic and 60% were non-Hispanic. All patients received calcium and vitamin D.
In the placebo group the rate of new vertebral fractures was 59 per 1,000 vs. 16 per 1,000 in the Evenity treated subjects. This represented a statistically significant 73% relative risk reduction in new vertebral fractures. The absolute risk reduction was 1.3% meaning that 77 women like those in the study would need to be treated for 1 year to prevent 1 new vertebral fracture.
There was no significant reduction in peripheral fractures in the Evenity treated subjects.
Bone Density Change after 12 Months Therapy with Evenity (red line)
There were no clinically significant side effects in the subjects treated with Evenity in the clinical trial. The FDA uses a legacy method from the pre-evidence based medicine days of assigning side effects to drugs based on the 5 most common adverse events that affected more than 2% of the Evenity subjects and were numerically more common in them. These will be designated as Evenity side effects by the FDA even though they did not occur more often statistically in the these subjects. By virtue of this outdated and non-scientific practice, Evenity will have at least 5 side effects one its label by the time it is cleared for marketing.
There was one subject who experienced atypical fracture of the femur and two with osteonecrosis of the jaw during the clinical trial while receiving Evenity. None of the placebo subjects experienced these. Both conditions have been observed to occur rarely in other osteoporosis therapies and spontaneously in people not on treatment for osteoporosis. Since these events occurred during this clinical trial, the US FDA will add a warning about these conditions on the drug’s label.