Get the break through and cure

The FDA Approves Denosumab for

Bone Loss in Osteoporosis
By Brenda Goodman

06/02/10 The U. S. Food and Drug Administration (FDA) have approved the drug Denosumab (Prolia), which
is the first biologically derived agent to treat bone loss caused by osteoporosis.

Regulators say the drug, which is injected under the skin every six months in a doctor’s office, is appropriate
for postmenopausal women who are at high risk for fractures – a group that includes those who have broken
a bone in the past because of osteoporosis, those who have multiple risk factors and those who can’t
tolerate other kinds of osteoporosis medications.

Like some other medications for osteoporosis, Denosumab (Prolia) works by preventing the breakdown of
bone by cells called osteoclasts.

But unlike bisphosphonates, including alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel)
and zolendronic acid (Reclast), which hasten cell death after they are ingested, Denosumab (Prolia) is a
monoclonal antibody that straitjackets a protein called RANKL that is important for the production, function
and survival of osteoclasts.

It is unclear whether Denosumab (Prolia) works better than older medications for bone loss, however,
because few head-to-head comparisons have been done.

A 2009 study of 7,868 women with osteoporosis who were followed for three years, Denosumab (Prolia)
reduced the risk of fractures at the spine and hip by 68 and 40 percent, respectively, compared to a placebo
injection. The drug also reduced the risk of other kinds of fractures by 20 percent compared to a placebo.
The study was published in the New England Journal of Medicine.

Experts say those results seem to be in line with the effects of zolendronic acid (Reclast) or even
teriparatide (Forteo) a hormone taken by daily injection that spurs the formation of new bone.

And in two trials, both recently published in the Journal of Bone and Mineral Research, that pitted
Denosumab (Prolia) against alendronate (Fosamax) in postmenopausal women for a year, found that
Denosumab (Prolia) reduced markers of bone turnover and slowed bone loss better than alendronate
(Fosamax), suggesting that it may work better than bisphosphonate pills.

"It's a very effective drug," says Sun deep Khosla, MD, of the Endocrine Research Unit of the Mayo Clinic's
College of Medicine in Rochester, Minn. "In terms of getting a drug that shuts down bone resorption, we
may be close to the best we can do."

Dr. Khosla wrote an editorial on Denosumab published in the August 20, 2009 New England Journal of
Medicine, and he reported no financial interest in the sales of this drug.

The bottom line, Dr. Khosla says, is that Denosumab will be good for patients who need a different option to
stem bone loss, but "it's not going to blow everything else we have out of the water, I don't think."

According to the FDA, the most commonly reported side effects associated with the drug include pain in the
back, arms and legs, muscle and bone pain, high cholesterol levels, and urinary tract infections.
Serious adverse events were rare but included infections that required hospitalization, low blood calcium,
and skin reactions including cellulites, rashes and eczema.

Denosumab (Prolia) is not cleared by the kidneys, which may make it a safer option for people who have
renal disease.

Dr. Khosla says Denosumab, which clears the body more quickly than bisphosphonates, may also be good
for women of childbearing age who don't want to risk exposing a developing fetus to the lingering effects of
a those drugs.

In a press release, Amgen, the company that developed Denosumab (Prolia), said it would charge a
wholesale price of $825 per injection for the drug, or $1,650 per year. By comparison, the wholesale price of
the infused form of the drug ibandronate (Boniva) is around $2,000 per year, while the generic drug
alendronate (Fosamax) can cost as little as $100 annually.