Women Had 6-Year BMD Rise With Denosumab

DENVER — The investigational agent denosumab continued to increase bone mineral density in osteoporotic postmenopausal women during 6 years of continuous use, based on the results of an extension of a phase II study including 412 women.

“Over a period of 6 years, continuous treatment with denosumab resulted in progressive gains in [bone mineral density] in postmenopausal women,” Dr. Paul Miller said at the annual meeting of the American Society for Bone and Mineral Research.

The 93 patients on denosumab 60 mg for 6 years had a continued increase in spine bone mineral density (BMD), with a mean cumulative increase from baseline in spine BMD of 13%. In addition, the reduction in resorption, as measured by serum C-telopeptide (CTX) levels, was sustained and plateaued over the course of continuous denosumab treatment.

Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density.

The study was sponsored by Amgen Inc., which is developing the drug. Dr. Miller reported significant financial relationships with several pharmaceutical companies that make osteoporosis treatments, including Amgen.

In the parent trial, 412 women were randomized to receive denosumab, open-label oral alendronate (70 mg/wk), or placebo. Denosumab was given subcutaneously either every 3 months (at 6 mg, 14 mg, or 30 mg) or every 6 months (at 14 mg, 60 mg, 100 mg, or 210 mg). All participants took daily oral supplements containing elemental calcium (1 g) and vitamin D (400 IU).

Postmenopausal women up to 80 years of age were eligible if they had a bone mineral density T score from −1.8 to −4.0 at the lumbar spine or from −1.8 to −3.5 at either the femoral neck or total hip. An upper limit of −1.8 was selected to include subjects with both osteopenia and osteoporosis. The 2-year data were published in Bone in 2008 (43:222-9).

At the end of the first 2 years, patients were reallocated. Denosumab-treated patients who continued the study were reassigned based on their randomization group at enrollment. Patients originally randomized to denosumab 6 mg or 14 mg (every 3 months) or 14 mg, 60 mg, and 100 mg (every 6 months) received denosumab 60 mg every 6 months for the next 2 years. This is the dose selected for phase III trials.

Patients originally randomized to denosumab 210 mg every 6 months received placebo for the next 2 years. Patients randomized to denosumab 30 mg every 3 months first received placebo for 12 months and then were subsequently re-treated with denosumab 60 mg every 6 months for the next 12 months. Alendronate patients discontinued alendronate therapy at this time. The placebo group was maintained.

In the extension phase of the study, all patients received denosumab 60 mg every 6 months for 2 more years. Measurements of bone mineral density of the lumbar spine, total hip, and femoral neck were performed by dual-energy x-ray absorptiometry throughout the trial.

The 16 patients who had been on placebo for 4 years and were switched to denosumab 60 mg every 6 months for the last 2 years had gains in spine BMD that were comparable to those observed in the first 2 years of the trial for patients on denosumab 60 mg every 6 months. Similar results were obtained for hip BMD. Patients on denosumab for 6 years had an average cumulative hip BMD increase of 6%.

“The forearm data … are interesting because forearm BMD increased in the denosumab groups, unlike the other antiresorptive agents that have consistently shown a decrease,” said Dr. Miller, whose group practice in Lakewood, Colo., specializes in the treatment of osteoporosis.

The adverse events seen during the extension were similar to those seen in the parent study.

DENVER — The investigational agent denosumab continued to increase bone mineral density in osteoporotic postmenopausal women during 6 years of continuous use, based on the results of an extension of a phase II study including 412 women.

“Over a period of 6 years, continuous treatment with denosumab resulted in progressive gains in [bone mineral density] in postmenopausal women,” Dr. Paul Miller said at the annual meeting of the American Society for Bone and Mineral Research.

The 93 patients on denosumab 60 mg for 6 years had a continued increase in spine bone mineral density (BMD), with a mean cumulative increase from baseline in spine BMD of 13%. In addition, the reduction in resorption, as measured by serum C-telopeptide (CTX) levels, was sustained and plateaued over the course of continuous denosumab treatment.

Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density.

The study was sponsored by Amgen Inc., which is developing the drug. Dr. Miller reported significant financial relationships with several pharmaceutical companies that make osteoporosis treatments, including Amgen.

In the parent trial, 412 women were randomized to receive denosumab, open-label oral alendronate (70 mg/wk), or placebo. Denosumab was given subcutaneously either every 3 months (at 6 mg, 14 mg, or 30 mg) or every 6 months (at 14 mg, 60 mg, 100 mg, or 210 mg). All participants took daily oral supplements containing elemental calcium (1 g) and vitamin D (400 IU).

Postmenopausal women up to 80 years of age were eligible if they had a bone mineral density T score from −1.8 to −4.0 at the lumbar spine or from −1.8 to −3.5 at either the femoral neck or total hip. An upper limit of −1.8 was selected to include subjects with both osteopenia and osteoporosis. The 2-year data were published in Bone in 2008 (43:222-9).

At the end of the first 2 years, patients were reallocated. Denosumab-treated patients who continued the study were reassigned based on their randomization group at enrollment. Patients originally randomized to denosumab 6 mg or 14 mg (every 3 months) or 14 mg, 60 mg, and 100 mg (every 6 months) received denosumab 60 mg every 6 months for the next 2 years. This is the dose selected for phase III trials.

Patients originally randomized to denosumab 210 mg every 6 months received placebo for the next 2 years. Patients randomized to denosumab 30 mg every 3 months first received placebo for 12 months and then were subsequently re-treated with denosumab 60 mg every 6 months for the next 12 months. Alendronate patients discontinued alendronate therapy at this time. The placebo group was maintained.

In the extension phase of the study, all patients received denosumab 60 mg every 6 months for 2 more years. Measurements of bone mineral density of the lumbar spine, total hip, and femoral neck were performed by dual-energy x-ray absorptiometry throughout the trial.

The 16 patients who had been on placebo for 4 years and were switched to denosumab 60 mg every 6 months for the last 2 years had gains in spine BMD that were comparable to those observed in the first 2 years of the trial for patients on denosumab 60 mg every 6 months. Similar results were obtained for hip BMD. Patients on denosumab for 6 years had an average cumulative hip BMD increase of 6%.

“The forearm data … are interesting because forearm BMD increased in the denosumab groups, unlike the other antiresorptive agents that have consistently shown a decrease,” said Dr. Miller, whose group practice in Lakewood, Colo., specializes in the treatment of osteoporosis.

The adverse events seen during the extension were similar to those seen in the parent study.

DENVER — The investigational agent denosumab continued to increase bone mineral density in osteoporotic postmenopausal women during 6 years of continuous use, based on the results of an extension of a phase II study including 412 women.

“Over a period of 6 years, continuous treatment with denosumab resulted in progressive gains in [bone mineral density] in postmenopausal women,” Dr. Paul Miller said at the annual meeting of the American Society for Bone and Mineral Research.

The 93 patients on denosumab 60 mg for 6 years had a continued increase in spine bone mineral density (BMD), with a mean cumulative increase from baseline in spine BMD of 13%. In addition, the reduction in resorption, as measured by serum C-telopeptide (CTX) levels, was sustained and plateaued over the course of continuous denosumab treatment.

Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density.

The study was sponsored by Amgen Inc., which is developing the drug. Dr. Miller reported significant financial relationships with several pharmaceutical companies that make osteoporosis treatments, including Amgen.

In the parent trial, 412 women were randomized to receive denosumab, open-label oral alendronate (70 mg/wk), or placebo. Denosumab was given subcutaneously either every 3 months (at 6 mg, 14 mg, or 30 mg) or every 6 months (at 14 mg, 60 mg, 100 mg, or 210 mg). All participants took daily oral supplements containing elemental calcium (1 g) and vitamin D (400 IU).

Postmenopausal women up to 80 years of age were eligible if they had a bone mineral density T score from −1.8 to −4.0 at the lumbar spine or from −1.8 to −3.5 at either the femoral neck or total hip. An upper limit of −1.8 was selected to include subjects with both osteopenia and osteoporosis. The 2-year data were published in Bone in 2008 (43:222-9).

At the end of the first 2 years, patients were reallocated. Denosumab-treated patients who continued the study were reassigned based on their randomization group at enrollment. Patients originally randomized to denosumab 6 mg or 14 mg (every 3 months) or 14 mg, 60 mg, and 100 mg (every 6 months) received denosumab 60 mg every 6 months for the next 2 years. This is the dose selected for phase III trials.

Patients originally randomized to denosumab 210 mg every 6 months received placebo for the next 2 years. Patients randomized to denosumab 30 mg every 3 months first received placebo for 12 months and then were subsequently re-treated with denosumab 60 mg every 6 months for the next 12 months. Alendronate patients discontinued alendronate therapy at this time. The placebo group was maintained.

In the extension phase of the study, all patients received denosumab 60 mg every 6 months for 2 more years. Measurements of bone mineral density of the lumbar spine, total hip, and femoral neck were performed by dual-energy x-ray absorptiometry throughout the trial.

The 16 patients who had been on placebo for 4 years and were switched to denosumab 60 mg every 6 months for the last 2 years had gains in spine BMD that were comparable to those observed in the first 2 years of the trial for patients on denosumab 60 mg every 6 months. Similar results were obtained for hip BMD. Patients on denosumab for 6 years had an average cumulative hip BMD increase of 6%.

“The forearm data … are interesting because forearm BMD increased in the denosumab groups, unlike the other antiresorptive agents that have consistently shown a decrease,” said Dr. Miller, whose group practice in Lakewood, Colo., specializes in the treatment of osteoporosis.

The adverse events seen during the extension were similar to those seen in the parent study.