Investigational Denosumab Has Minimal Adverse Effects

PHILADELPHIA — Denosumab, an investigational antibody in phase III studies as a treatment to maintain bone density and cut bone metastases, has so far shown better safety than intravenous bisphosphonates, the main comparator drugs.

Results are available from more than 4,500 patients who were treated with denosumab for any indication, including both bone metastases and as osteoporosis treatment, and there have been no cases of renal toxicity and one case of symptomatic hypocalcemia, Dr. Allan Lipton said at a conference on skeletal complications of malignancy. In contrast, both renal toxicity and hypocalcemia have been safety issues for intravenous bisphosphonates, said Dr. Lipton, professor of medicine at Hershey (Pa.) Medical Center.

Denosumab is being developed by Amgen, which sponsored all of the clinical studies. Dr. Lipton is a consultant to and has received honoraria from Amgen.

Compared with bisphosphonates, denosumab also seems to cause fewer acute-phase reactions with flu-like symptoms. In a phase II study of 255 patients with bone metastases from breast cancer led by Dr. Lipton, patients treated with denosumab had an 8% incidence of a flu-like, acute-phase reaction during the first 3 days after treatment start, vs. a 33% rate in patients randomized to treatment with an intravenous bisphosphonate. During the first month after treatment started, acute-phase reactions occurred in 26% of the denosumab patients and 49% of those on an intravenous bisphosphonate.

Denosumab is a fully human monoclonal antibody that binds to and blocks the ligand that stimulates osteoclast-mediated bone resorption. In this way, the drug cuts the rate of bone resorption, and may also have other actions that interfere with bone metastasis.

Reports from two phase II studies of denosumab for treating patients with bone metastases from solid tumors showed that the drug was at least as effective as an intravenous bisphosphonate for reducing a plasma marker of bone resorption. These results, as well as findings from osteoporosis treatment studies, have led to several phase III trials in patients with bone metastases where denosumab's efficacy is again being compared with intravenous bisphosphonates. An additional phase III study is looking at denosumab's ability to prevent bone metastases compared with placebo, Dr. Lipton said at the meeting, jointly sponsored by the Paget Foundation and the University of Michigan.

The dosage used in most of the phase III studies is 120 mg subcutaneously every 4 weeks. In phase II studies, this dosage was more effective for suppressing skeletal-related events than 30 mg subcutaneously every 4 weeks, but the 120-mg dose avoided the asymptomatic hypocalcemia seen in patients getting 180 mg subcutaneously every 4 weeks, Dr. Lipton said.

PHILADELPHIA — Denosumab, an investigational antibody in phase III studies as a treatment to maintain bone density and cut bone metastases, has so far shown better safety than intravenous bisphosphonates, the main comparator drugs.

Results are available from more than 4,500 patients who were treated with denosumab for any indication, including both bone metastases and as osteoporosis treatment, and there have been no cases of renal toxicity and one case of symptomatic hypocalcemia, Dr. Allan Lipton said at a conference on skeletal complications of malignancy. In contrast, both renal toxicity and hypocalcemia have been safety issues for intravenous bisphosphonates, said Dr. Lipton, professor of medicine at Hershey (Pa.) Medical Center.

Denosumab is being developed by Amgen, which sponsored all of the clinical studies. Dr. Lipton is a consultant to and has received honoraria from Amgen.

Compared with bisphosphonates, denosumab also seems to cause fewer acute-phase reactions with flu-like symptoms. In a phase II study of 255 patients with bone metastases from breast cancer led by Dr. Lipton, patients treated with denosumab had an 8% incidence of a flu-like, acute-phase reaction during the first 3 days after treatment start, vs. a 33% rate in patients randomized to treatment with an intravenous bisphosphonate. During the first month after treatment started, acute-phase reactions occurred in 26% of the denosumab patients and 49% of those on an intravenous bisphosphonate.

Denosumab is a fully human monoclonal antibody that binds to and blocks the ligand that stimulates osteoclast-mediated bone resorption. In this way, the drug cuts the rate of bone resorption, and may also have other actions that interfere with bone metastasis.

Reports from two phase II studies of denosumab for treating patients with bone metastases from solid tumors showed that the drug was at least as effective as an intravenous bisphosphonate for reducing a plasma marker of bone resorption. These results, as well as findings from osteoporosis treatment studies, have led to several phase III trials in patients with bone metastases where denosumab's efficacy is again being compared with intravenous bisphosphonates. An additional phase III study is looking at denosumab's ability to prevent bone metastases compared with placebo, Dr. Lipton said at the meeting, jointly sponsored by the Paget Foundation and the University of Michigan.

The dosage used in most of the phase III studies is 120 mg subcutaneously every 4 weeks. In phase II studies, this dosage was more effective for suppressing skeletal-related events than 30 mg subcutaneously every 4 weeks, but the 120-mg dose avoided the asymptomatic hypocalcemia seen in patients getting 180 mg subcutaneously every 4 weeks, Dr. Lipton said.

PHILADELPHIA — Denosumab, an investigational antibody in phase III studies as a treatment to maintain bone density and cut bone metastases, has so far shown better safety than intravenous bisphosphonates, the main comparator drugs.

Results are available from more than 4,500 patients who were treated with denosumab for any indication, including both bone metastases and as osteoporosis treatment, and there have been no cases of renal toxicity and one case of symptomatic hypocalcemia, Dr. Allan Lipton said at a conference on skeletal complications of malignancy. In contrast, both renal toxicity and hypocalcemia have been safety issues for intravenous bisphosphonates, said Dr. Lipton, professor of medicine at Hershey (Pa.) Medical Center.

Denosumab is being developed by Amgen, which sponsored all of the clinical studies. Dr. Lipton is a consultant to and has received honoraria from Amgen.

Compared with bisphosphonates, denosumab also seems to cause fewer acute-phase reactions with flu-like symptoms. In a phase II study of 255 patients with bone metastases from breast cancer led by Dr. Lipton, patients treated with denosumab had an 8% incidence of a flu-like, acute-phase reaction during the first 3 days after treatment start, vs. a 33% rate in patients randomized to treatment with an intravenous bisphosphonate. During the first month after treatment started, acute-phase reactions occurred in 26% of the denosumab patients and 49% of those on an intravenous bisphosphonate.

Denosumab is a fully human monoclonal antibody that binds to and blocks the ligand that stimulates osteoclast-mediated bone resorption. In this way, the drug cuts the rate of bone resorption, and may also have other actions that interfere with bone metastasis.

Reports from two phase II studies of denosumab for treating patients with bone metastases from solid tumors showed that the drug was at least as effective as an intravenous bisphosphonate for reducing a plasma marker of bone resorption. These results, as well as findings from osteoporosis treatment studies, have led to several phase III trials in patients with bone metastases where denosumab's efficacy is again being compared with intravenous bisphosphonates. An additional phase III study is looking at denosumab's ability to prevent bone metastases compared with placebo, Dr. Lipton said at the meeting, jointly sponsored by the Paget Foundation and the University of Michigan.

The dosage used in most of the phase III studies is 120 mg subcutaneously every 4 weeks. In phase II studies, this dosage was more effective for suppressing skeletal-related events than 30 mg subcutaneously every 4 weeks, but the 120-mg dose avoided the asymptomatic hypocalcemia seen in patients getting 180 mg subcutaneously every 4 weeks, Dr. Lipton said.