* Infection risk at forefront
* Panel expected to recommend approval
By Deena Beasley
LOS ANGELES, Aug 9 Thursday's U.S. Food and
Drug Administration advisory panel review of denosumab, Amgen
Inc's (AMGN.O) experimental osteoporosis drug, will likely
center on safety, particularly the risk of serious infections.
Denosumab -- to be sold under the brand name Prolia -- is
seen as Amgen's best hope of jump-starting growth now that
safety concerns have deflated sales of its flagship anemia
The biotech company filed in December for approval of
denosumab as a treatment for post-menopausal osteoporosis and
for treating and preventing bone loss in patients undergoing
hormone ablation for either prostate or breast cancer.
Given denosumab's easy administration and infrequent
dosing, "a lot (of osteoporosis patients) will end up being
treated with this drug right off the bat," said Dr.John Adams,
an endocrinologist at the University of California, Los Angeles
who was not involved in denosumab's development.
"We do think that ultimately it (denosumab) is going to get
approved," said Cowen & Co analyst Craig Gordon. "I think
what's unclear is the extent of post-marketing commitments
Amgen will be required to do."
BRIEFING DOCUMENTS ON TUESDAY
Investors will get a sense of the FDA's thinking on
Tuesday, when the agency is expected to release internal memos
with a preliminary analysis of Amgen's denosumab data.
FDA reviewers will present the views to the advisory panel
on Thursday before the outside experts make recommendations on
the drug. The agency usually follows committee advice when
making final approval decisions.
Denosumab is also being developed for treating bone loss in
BMO Capital Markets analyst Jason Zhang estimated combined
sales of denosumab in the osteoporosis and oncology markets of
$2.4 billion by 2012.
Trials of the drug in post-menopausal women with
osteoporosis found that it reduced the risk of spine fractures
by nearly 70 percent, but some studies showed a higher rate of
serious skin infections that required hospitalization.
Amgen is banking on the impressive clinical data, along
with a patient-friendly dosing schedule of twice-yearly
injections to help it compete with existing osteoporosis drugs,
some of which are already available as low-cost generics.
RISK MANAGEMENT PLAN?
Denosumab is a bioengineered antibody that targets RANK
ligand, a protein involved with bone-destroying cells called
In addition to infection risk, the FDA committee is also
likely to discuss the risk of cataracts, since an imbalance of
incidence was seen in one trial, and the risk of a rebound in
bone turnover markers, said Gordon at Cowen & Co.
"We expect the FDA to basically concede efficacy and mostly
just address safety," he said.
The FDA may approve the drug with a required risk
management plan to minimize side effects, an increasingly
common scenario for new medicines. The agency can mandate
post-approval studies, distribution limits or other measures.
Bad news for the stock would include a recommendation for a
stringent risk management plan, which could limit the
likelihood that a doctor would prescribe the drug.
In the best case, the panel would simply call for active
surveillance of side effects, Gordon said.
Dr. Adams said the risk of infection with denosumab could
be mitigated by ensuring that patients are getting sufficient
vitamin D before they are started on the drug.
"RANK ligand is made by the body's lymphocytes -- part of
the immune system," he said. "When you give this drug
(denosumab) to someone who is vitamin D deficient, they are
In the cancer setting, where a much higher dose of the drug
is used, questions have been raised about the risk of
osteonecrosis -- or deterioration -- of the jaw, a serious side
effect associated with some other osteoporosis drugs.
The FDA is slated to issue a decision on the denosumab
marketing application by Oct. 19, but many on Wall Street
expect that the deadline could be missed given the agency's
recent track record of delayed decisions.
(Additional reporting by Lisa Richwine in Washington; Editing