A panel of experts commissioned by the U.S. Food and Drug Administration (FDA) has given a mixed review to a new kind of osteoporosis drug, called denosumab.
Amgen, the company that makes the drug, has asked the FDA to approve denosumab, which is given by injection every six months, to prevent and treat postmenopausal osteoporosis, and to prevent and treat bone loss in breast and prostate cancer patients.
The 15-member Advisory Committee for Reproductive Health Drugs voted unanimously to support the approval of denosumab to treat osteoporosis, but the experts voted 12 to 3 against using the drug for prevention, citing questions about long-term safety.
The FDA is not required to follow the recommendation of its advisors, though it frequently does.
Denosumab, a human monoclonal antibody which may be sold under the brand name Prolia, would be the first biologic drug approved to treat bone loss.
Bone is a dynamic tissue that’s constantly being built up by cells called osteoblasts and torn down by cells called osteoclasts. With age, the balance between these two processes can shift, and more bone is torn down than built.
Under a microscope, the resulting bone looks a little bit like Swiss cheese; it has more holes and is weaker than healthy tissue.
Existing drugs that treat bone loss, called bisphosphonates, are drawn to bone tissue where they are ingested by osteoclasts. Once inside these cells they disrupt their normal function to slow or stop their activity.
Denosumab, however, works by muting the chemical messenger that spurs bone breakdown.
Scientifically speaking, the drug prevents the formation of osteoclasts by blocking the action of the receptor activator of nuclear factor-kappa beta ligand, or RANKL, a signaling molecule that stimulates a cascade of reactions related to bone formation, immune function and inflammation.
In addition to its role in osteoporosis, overproduction of RANKL, which is part of the tumor necrosis factor family of cytokines, has been linked with diseases that involve the erosion of bone, such as rheumatoid arthritis and psoriatic arthritis; and it is already being studied as an adjunct treatment to prevent structural damage in these conditions.
In the clinical studies, denosumab has been shown to prevent bone loss and fractures better than a placebo, and it appeared to be at least as effective at preventing and treating bone loss and fractures as bisphosphonate medications.
Study participants taking denosumab had more serious infections, including infections of the skin, ear, abdominal system and urinary tract, than those who took a placebo.
The risk of cancer related to the use of the drug is unknown because it was not possible to test this drug, which is a human antibody, in another species.
Thus far, there have been no cases of osteonecrosis, or “bone death,” in people taking denosumab. Osteonecrosis is a rare but dangerous side effect of bisphosphonate therapy.
Denosumab is also shorter acting than bisphosphonates and is not cleared by the kidneys, something that may make it safer for people who have renal disease.