2nd UPDATE:FDA Panel Backs Denosumab As Osteoporosis Treatment
13 August 2009 - 11:13PM
Dow Jones News
A U.S. Food and Drug Administration panel on Thursday
unanimously backed the use of denosumab, a proposed Amgen Inc.
(AMGN) drug, to treat osteoporosis in postmenopausal women, but
said use of novel product should initially be limited until more is
known about long-term side effects.
The panel also overwhelmingly suggested the product not be used
to prevent osteoporosis in women with low bone mass who are at risk
of developing osteoporosis and split on use of the product in
certain breast and prostate-cancer patients.
Still, investors have high expectations for denosumab to grab a
share of the roughly $7 billion market for osteoporosis drugs,
which has helped boost Amgen's stock price by about 30% in recent
months. Approval of denosumab, which would be injected twice
yearly, is key for Amgen's growth.
About 10 million Americans have osteoporosis, or bone weakness
that places people at high risk of suffering bone fractures, while
an additional 34 million have low bone mass that puts them at risk
for developing osteoporosis.
The panel voted 15-to-0 on a question that asked if there were a
population of postmenopausal women with osteoporosis in which the
benefit of treatment with denosumab is likely to outweigh the
risks,which amounts to a recommendation that the FDA approve the
drug as an osteoporosis treatment.
However, the panel said treatment should be limited to women
with a history of fracture or who are at high risk for fracture.
Panel members also said women should try other treatments before
denosumab until there are more long-term safety data about the
product and whether it affects the immune system and raises risks
for serious infections and cancer.
The panel voted 13 to 2 against a question that asked whether
there was a population of women with low bone mineral density in
which the benefit of prevention of osteoporosis with denosumab is
likely to outweigh the risks.
The panel split on the use of the drug to treat bone loss
associated with hormone treatment for breast and prostate cancer
patients with the panel backing use of the drug for certain
prostate cancer patients and rejecting it for women being treated
with aromatase inhibitors.
While the FDA said denosumab was effective at increasing
bone-mineral density and reducing the risk of fractures by nearly
70% over three years compared to women not taking the drug, the
agency raised concerns about the product's impact on the immune
system and whether that, in turn, raises risks for serious
infections and cancer.
In order to treat or prevent osteoporosis, denosumab is designed
to inhibit a protein known as RANK Ligand that is involved with
bone destruction. However, the same protein also plays a role in
the body's immune system.
The agency said clinical trials involving denosumab showed a
slightly higher rate of serious infections and the development of
certain types of cancer. The agency also said there is a "potential
for tumor progression in patients with cancer." While clinical data
showed numerical differences for infections and cancer, the data
didn't reach statistical significance, meaning the differences
could be a chance finding.
Amgen officials said there was no evidence seen in clinical
trials that denosumab suppresses the immune system and increases
risks for infections and cancer.
Catherine Stehman-Breen, Amgen's vice president of global
development, told the panel that denosumab has a "favorable safety
profile," with most adverse events being "mild-to-moderate" as well
as balanced between patients who received denosumab and patients
who received placebo.
Amgen officials said they already have long-term studies in
progress that can be used to track safety issues. They also said
they plan additional studies if denosumab were to be approved.
The FDA usually follows its panel's advice but isn't required to
do so. The agency has a deadline to make by mid-October but that
timetable could be delayed if the agency decides to implement a
post-marketing safety plan formally known as a Risk Evaluation and
Mitigation Strategy, or REMS.
If approved, the drug would be sold under the brand name
Prolia.
Denosumab is the first type of drug in its class and acts in a
different manner than many other drugs, such as Boniva, Fosamax,
and Reclast, that are considered bisphosphonates in order to
prevent bone loss. Bisphosphonates, which are delivered orally or
through an infusion, have their own side effects, including a risk
of rare jaw decay problem.
Ethel Siris, director of the Toni Stabile Osteoporosis Center at
Columbia University who presented on behalf of Amgen, said more
than half of patients who are prescribed daily oral pills aren't
taking them more than a year later partly because of
gastrointestinal side effects.
"Adherence is a critical issue" in treating osteoporosis, Siris
said, noting that doctors can determine if patients are compliant
with medication if they have to come in to the office to receive
their medication.
Reclast, made by Novartis AG (NVS), is an infusion that is given
once a year and would be the most direct competitor to denosumab,
if approved. That drug has a wholesale cost of $1,000; the generic
version of Fosamax is less than $20 a month. Amgen said it was too
early to discuss pricing details.
-By Jennifer Corbett Dooren, Dow Jones Newswires; 202-862-9294;
jennifer.corbett@dowjones.com