The committee for medicinal products for human use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion in the marketing authorisation of Prolia (denosumab) for the treatment of bone loss associated with long-term systemic glucocorticoid therapy in adult patients at increased risk of fracture.
“Today’s positive opinion by the CHMP is an important step for Prolia in helping patients suffering from bone loss associated with systemic glucocorticoid therapy,” says Sean E Harper executive vice president of research and development at Amgen. “Chronic use of glucocorticoids has been associated with an increase in spine and hip fractures, and, if approved, an expanded use of Prolia will provide patients and physicians across much of Europe with a new treatment option for this serious condition.”
Glucocorticoid medications, which are used to treat many inflammatory conditions such as chronic obstructive pulmonary disorder (COPD), asthma, multiple sclerosis and rheumatoid arthritis, can cause significant side effects, including bone loss.
The CHMP recommendation is supported by a Phase 3 randomised, double-blind, double-dummy, active-controlled study evaluating the safety and efficacy of Prolia compared with risedronate in patients receiving glucocorticoid treatment. The study included two patient groups: those on sustained glucocorticoid therapy, and those newly initiating glucocorticoid therapy. The study met the primary endpoint (percent change from baseline in lumbar spine bone mass density at 12 months, assessing non-inferiority) and all secondary endpoints (the percent changes from baseline in lumbar spine and total hip bone mass density at 12 and 24 months, assessing superiority).
Study results showed that, in patients on sustained glucocorticoid therapy, Prolia treatment led to greater gains in bone mass density, compared with risedronate, both at the lumbar spine (4.4% vs. 2.3%, respectively) and total hip (2.1% vs. 0.6%, respectively). Similarly, in patients newly initiating glucocorticoid therapy, Prolia treatment led to greater increases in bone mass density, compared with risedronate, both at the lumbar spine (3.8% vs. 0.8%, respectively) and total hip (1.7% vs. 0.2%, respectively).
Adverse events and serious adverse events were similar between treatment groups and consistent with the known safety profile of Prolia. No serious adverse events were reported with a subject incidence of two% or greater in either treatment group.
The CHMP positive opinion will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union. Norway, Iceland and Liechtenstein, as members of the European Economic Area, will take corresponding decisions based on the decision of the European Commission.
The US Food and Drug Administration is currently reviewing a supplemental Biologics License Application for this expanded indication.