Amgen drug slows bone loss in cancer patients

By Deena Beasley

LOS ANGELES (Reuters) – Amgen Inc. said on Sunday that
early results from mid-stage trials of its experimental drug
denosumab show that it works at least as well as current
therapies to limit bone loss in patients with late-stage
cancer.

A study investigator said that the product, seen as one of
Amgen’s most promising, was not able to show at this point in
time that it is more effective than existing drugs, called
bisphosphonates.

“There are hints that this drug is very, very active. We
would hope that a Phase III trial would show that it works
better than bisphosphonates, but we can’t say that now,” said
Dr. Allan Lipton, professor of medicine/oncology at Penn State
University and an investigator in both Amgen studies.

Each year, more than 400,000 U.S. cancer patients, often
those with breast or prostate cancer, have the disease spread
to their bones, leading to pain, fractures and the need for
surgery.

Currently, they are treated with intravenous
bisphosphonates drugs, including Novartis AG’s Zometa and
Aredia, which help in about a third of cases, Lipton said.

Denosumab, which is also being developed for treatment of
osteoporosis, is an antibody designed to turn off the genetic
switch that triggers bone-chewing cells called osteoclasts.

In the first study, which involved different doses of
denosumab in breast cancer patients not previously treated with
bisphosphonates, researchers saw as much as an 82 percent
decrease in a urinary marker that tracks bone loss after 13
weeks.

Bisphosphonate-treated patients saw a 79-percent drop in
the marker, said Amgen, which reported the results at a meeting
of the American Society of Clinical Oncology in Atlanta

In a separate Phase III study of 49 prostate, breast, and
multiple myeloma patients already on IV bisphosphonates but not
responding to them, twice as many patients achieved normal
levels of bone turnover when they were switched to denosumab,
the company said.

After 13 weeks, 76 percent of denosumab patients achieved
normal levels of bone turnover, compared with 38 percent of
patients who remained on the IV bisphosphonate,

Side effects of denosumab included nausea, vomiting,
weakness and diarrhea, while side effects for
bisphosphonate-treated patients included infection-induced
fever, joint pain, and bone pain.

Zometa and Aredia, as well as oral bisphosphonates, have
been linked to a serious side effect known as osteonecrosis, or
death of areas of bone in the jaw.

Preliminary data on denosumab, which has a different
mechanism of action than those drugs, show no indication of a
similar problem, said Amgen spokeswoman Kerry Beth Daly.

She added that the company’s clinical program is ongoing
and the drug’s safety profile won’t be clear until pivotal
Phase III data are out.

“The hope in the future is that this class of drugs may be
able to prevent bone metastases,” Lipton said.

Amgen is currently conducting several trials of denosumab,
including studies of bone cancer prevention. The first Phase
III results for the drug, in osteoporosis, are expected in
2008.