Denosumab, A New Osteoporosis Mitigation Drug
What is Denosumab?
Denosumab is a monoclonal antibody that prevents the formation of a protein called RANKL in osteoclasts. Osteoclasts are the cells that the body manufactures to break down bone for eventual replacement. Think of this as the body's bone remodeling process. Denosumab is currently in trials, but the results of these trials are so far encouraging.
Denosumab has a different way of working than currently marketed osteoporosis drugs including Fosamax (Merck), Actonel (Proctor & Gamble Pharmaceuticals), Forteo (Eli Lilly), Reclast (Novartis) and Boniva (Roche). The down side to these other drugs is the frequency of injection/administration ranging from daily to weekly doses. Denosumab, by contrast, would be injected twice a year.
One trial* included 7,868 women, aged 60 to 90, with moderate to severe osteoporosis. A second trial, included 912 men with prostate cancer at increased spinal fracture risk due to cancer hormone therapy. Both trials are double-blind studies in which half those tested were given a placebo and the other half denosumab.
In the women's trial 68% of those receiving the drug had reduced spine fractures and 40% fewer hip fractures. In the men's trial 62% had fewer spine fractures as compared to those men given a placebo.
* As with any new drug trials are paid for by the manufacturer.
How it Works.
Fosamax, Actonel, Reclast and Boniva all prevent the formation of osteoclasts.
Denosumab, by contrast, binds to a protein called RANKL which is used to activate osteoclasts in the body. Since denosumab binds to this protein it's use by osteoclasts to break down bone is greatly reduced. The drug does not prevent the formation of osteoclasts, unlike the above mentioned drugs, just inhibits their effectiveness.
RANKL also has a role in TCell immune response. For this reason the FDA may require Amgen to continually report on denosumab even if approved for use by prescription.
Denosumab may be responsible for eczema in some trial participants.
The drug will also have to be closely monitored for long term immune response effects. This is because RANKL is a component of the TCell outer wall.
Books on Monoclonal Antibodies
Advantages of Denosumab
In the two trials Denosumab did not demonstrate a risk of infection or cancer, unlike other osteoporosis drugs. Denosumab also wasn't linked to osteonecrosis of the jaw, sometimes called "jawbone death."
Denosumab's safety profile "appeared excellent" in the prostate cancer study; the study was the first large study of spinal fracture prevention in men taking prostate cancer hormone treatment.
Finally, denosumab can be given as an injection only twice a year. This means patients are less likely to forget or miss a dose and can be given the drug by a nurse or nurse practitioner.
Disadvantages of Denosumab
Eczema and severe cases of a skin infection called cellulitis were more common in women taking denosumab in the first study, though the reasons for this remain unclear.
Also, because this is a new drug based on monoclonal anti-body research, with high cost per unit to produce, the drug may be cost prohibitive to all, but the few who can afford it*.
Denosumab's effectiveness may fall off to zero levels after three to four years. This is true of all other osteoporosis drugs currently on the market.
* A spokesperson for Amgen promised that the company would do it's best to make the product affordable.
Amgen ("portmanteau" of Applied Molecular Genetics) is a featured company in Jim Collin's book "Built to Last."
Amgen is a publicly traded company located in Thousand Oaks California. It currently employees 14,000 persons making it the second largest employer in Ventura County; second only to the United States Navy in the area.
The author of this article does not work for or own stock in (either directly or indiretly) Amgen Corporation, but does find the company's philosophy and history of revolutionary drugs fascinating.
- Osteoclast: A cell who's function is to destroy bone.
- Osteoblast: A cell who's function is to create bone.
- Monoclonal: Replication of a cell from one ancestral cell. The cell is "encourage" to repeatedly divide; in the process creating many new cells.
- Antibodies: A protein that binds to specific foreign bodies for the purpose of targeting them for elimination from the body. Antibodies typically bind to viruses and bacteria. Antibodies are produced by the white blood cell.
- Antigen: Antibody Generator. A substance that prompts the generation of Antibodies.