http://www.asco.org/portal/site/ASCO...reutersid=4904#
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.
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