New Osteoporosis Drugs in the Works

Two experimental osteoporosis drugs are getting attention
from bone experts -- and may become the first biologic drugs to treat
osteoporosis.

The drugs are called denosumab and odancatib. Results from their latest
clinical trials, presented this week in Montreal at the annual meeting of the
American Society for Bone and Mineral Research, show that the drugs boosted
bone mineral density in postemenopausal women with osteoporosis.

Denosumab and odanacatib are "totally, completely new" ways of
approaching osteoporosis, says Susan Bukata, MD, an orthopaedic surgeon and
associate professor who directs the University of Rochester's Center for Bone
Health.

"This is the new frontier in osteoporosis. This is the step into
biologics for osteoporosis treatment ," Bukata tells WebMD. She
predicts that denosumab or odanacatib probably won't be the first osteoporosis
treatments that doctors prescribe for most patients, and she says cost may be a
factor in how widely the new drugs get used, if approved by the FDA.

How the New Drugs Work

Denosumab and odanacatib are both biologic drugs that target osteoclasts,
which are cells that tear down bone to make way for new bone.

Your bones don't just sit there; they're constantly being remodeled.
Osteoclasts are the wrecking crew; other cells, called osteoblasts, are the
bone builders.

After you reach peak bone mass at about age 30, the balance between the bone
breakdown and bone buildup shifts, favoring bone loss. Age -- and, for women,
menopause -- tilts the balance further toward bone loss. In osteoporosis, the
bones have become dangerously weak.

"As you age, things slow down," Bukata explains. "Unfortunately,
for a lot of people, bone-building capacity slows down a little bit more than
their bone-loss capacity."

The basic idea behind the new osteoporosis drugs is to rebalance bone loss
and bone building so that those two processes "either stay in balance or,
in fact, allow the osteoblasts to catch up a little bit," says Bukata.
"By adding these agents, we are able to push things the way a younger
person manages bone."

Denosumab's Clinical Trial

Denosumab is a monoclonal antibody given by injection twice a year. It
targets a chemical called RANK ligand, which osteoclasts need to do their
job.

Denosumab has finished its phase lll clinical trials, the last set of trials
needed before submitting a drug to the FDA for approval.

In those trials, postmenopausal women with low bone mineral density either
got a shot of denosumab every six months or took alendronate (the active
ingredient in Fosamax ) every week.

A year later, bone mineral density in the lumbar spine and in the hip had
improved more for the denosumab group than for the alendronate group.

Bukata notes that because biologic drugs affect the immune system,
researchers keep a close eye on infection rates for biologic drugs, but
infections weren't more common with denosumab in the trial.

Cancer risk is another thing
that researchers would check on, but tumors weren't more common with denosumab
than with alendronate, according to a news release from Amgen, the drug company
which makes denosumab.

It's also important that denosumab mainly affects the skeleton and not other
body systems, says Buikata, who hasn't seen any worrisome data for
denosumab.

"I and others fully expect denosumab up in front of the FDA soon,"
says Bukata, predicting that denosumab will get FDA approval. "Their data
has been good, there have been very solid studies, very open reporting all
along the way."

Bukata likes the fact that denosumab is given by injection twice a year, and
that those injections don't have to be given by a doctor. That should help with
compliance, notes Bukata.

Odanacatib's Trial

Odanacatib takes a different biologic tactic. It targets an enzyme calledcathepsin K, in order to reduce osteoclast activity.

Odanacatib isn't as far along in the development process as denosumab;
odanacatib's phase lll trial is just getting under way. But two-year results
from odanacatib's phase llb trial show promise.

"That data definitely made me pay much more attention this drug,"
says Bukata.

In the trial, postmenopausal women with osteoporosis took an odanacatib pill
or a placebo once a week. Patients don't have to take odanacatib with a meal
and they don't have to stand or sit after taking it, notes Ron Rogers, a
spokesperson for Merck, the drug company that makes odanacatib.

Two years later, women who took a weekly 50-milligram odanacatib pill had
significant gains in bone mineral density in their lumbar spine and hip. As
expected, the placebo didn't help bone mineral density.

Odanacatib's phase lll trials will test odanacatib for fracture prevention
in postmenopausal women with osteoporosis. That trial's results may be four
years away, according to Arthur Santora, MD, PhD, Merck's executive director of
clinical research.

Bukata says she'll be watching odanacatib's trial with interest.

"Does the bone mass gain continue to hold up in additional years on the
medication? If it does, that makes this drug very appealing," says Bukata.
"The other thing is, how did the patients tolerate it? What are the side
effects that come with it?"

In odanacatib's phase 11b trial, the drug was "generally favorable,"
report the researchers. Skin
rashes , which Merck officials say sidelined another company's cathepsin K
inhibitor, didn't stand out in the odanacatib group.

Drugs' Future

Will denosumab and odanacatib catch on, if approved by the FDA? Bukata says
that depends on how they stack up against current osteoporosis drugs.

"They have to be as good as what we have, if not better," says
Bukata. She's not just talking about effects on bones, but also side effects,
patient compliance in taking the drugs, and cost.

For instance, Bukata says that if patients are getting good results from
older osteoporosis drugs, they would "have to have a good reason" to
switch to a newer type of drug, especially if the new drug is more
expensive.

Bukata predicts that most osteoporosis patients would still start treatment
with bisphosphonates or other established types of
osteoporosis drugs and try newer biologic drugs if other treatments don't
work. Patients who can't take current osteoporosis drugs, such as people with
poor kidney function, might start out on biologic drugs, Bukata says.

Bukata has no ties to Amgen or Merck. She does lecture on osteoporosis for
another drug company, Eli Lilly, on a limited basis.

By Miranda Hitti
Reviewed by Louise Chang
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