FREEDOM Extension: Denosumab Remains Safe, Effective up to 6 Years

CHICAGO – Denosumab remained well-tolerated, safe, and effective for maintaining reduced bone turnover and for increasing bone mineral density after 6 years of continuous use in 2,343 postmenopausal women with increased fracture risk due to osteoporosis.

These findings come from the first 3 years of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis) extension trial.

The fully human monoclonal antibody also led to significant gains in bone mineral density in a "crossover" group of 2,207 women who received placebo during the original FREEDOM trial – a pivotal trial published in 2009 that demonstrated a favorable risk/benefit profile for denosumab (N. Engl. J. Med. 2009;361:756-65).

The agent subsequently received Food and Drug Administration approval for the treatment of postmenopausal women with osteoporosis and an increased fracture risk.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group.

During the open-label active treatment extension trial, which was designed to investigate the efficacy and safety of the drug for up to 10 years, participants received 60 mg of denosumab as a subcutaneous injection every 6 months along with daily supplemental calcium and vitamin D. In the first 3 years of the extension trial, those in the long-term treatment group experienced additional, statistically significant increases in bone mineral density (cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip), and those in the crossover group experienced significant mean gains in bone mineral density that were similar to those seen initially in the FREEDOM trial active treatment group (9.4% at the lumbar spine and 4.8% at the total hip), Dr. Jacques P. Brown reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

The gains seen in the active treatment group in the FREEDOM trial at 3 years were 10.1% at the lumbar spine and 5.7% at the total hip, said Dr. Brown of Laval University, Quebec City.

Measures of serum carboxy-terminal telopeptide (CTX), which is a marker of bone resorption, demonstrated "a profound reduction in bone resorption" appearing rapidly and similarly after the first treatment in the cross-over group, and after the seventh treatment in the long-term treatment group – with the "characteristic attenuation observed at the end of the dosing period," Dr. Brown said.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group. Fracture incidence also remained low in the long-term group in the extension trial, he said, noting that adverse events and serious adverse events also did not increase over time in the extension trial, and there were no "significant imbalances between the groups."

Osteonecrosis of the jaw occurred in two patients in both the long-term and crossover treatment groups; in the crossover group, both cases resolved completely within the follow-up period, and one of those patients had continued on treatment. The cases in the long-term treatment group remained unresolved at the time of Dr. Brown’s report.

These interim findings from the FREEDOM extension trial demonstrate that denosumab treatment for up to 6 years lead to continued improvement in women on long-term treatment, and that treatment for up to 3 years in the crossover group largely reproduced the observations in the original FREEDOM denosumab group, Dr. Brown concluded.

Dr. Brown disclosed having various relationships with Abbott, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier, and Warner Chilcott. Other authors on the study also disclosed various relationships with these and/or other pharmaceutical companies.

CHICAGO – Denosumab remained well-tolerated, safe, and effective for maintaining reduced bone turnover and for increasing bone mineral density after 6 years of continuous use in 2,343 postmenopausal women with increased fracture risk due to osteoporosis.

These findings come from the first 3 years of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis) extension trial.

The fully human monoclonal antibody also led to significant gains in bone mineral density in a "crossover" group of 2,207 women who received placebo during the original FREEDOM trial – a pivotal trial published in 2009 that demonstrated a favorable risk/benefit profile for denosumab (N. Engl. J. Med. 2009;361:756-65).

The agent subsequently received Food and Drug Administration approval for the treatment of postmenopausal women with osteoporosis and an increased fracture risk.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group.

During the open-label active treatment extension trial, which was designed to investigate the efficacy and safety of the drug for up to 10 years, participants received 60 mg of denosumab as a subcutaneous injection every 6 months along with daily supplemental calcium and vitamin D. In the first 3 years of the extension trial, those in the long-term treatment group experienced additional, statistically significant increases in bone mineral density (cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip), and those in the crossover group experienced significant mean gains in bone mineral density that were similar to those seen initially in the FREEDOM trial active treatment group (9.4% at the lumbar spine and 4.8% at the total hip), Dr. Jacques P. Brown reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

The gains seen in the active treatment group in the FREEDOM trial at 3 years were 10.1% at the lumbar spine and 5.7% at the total hip, said Dr. Brown of Laval University, Quebec City.

Measures of serum carboxy-terminal telopeptide (CTX), which is a marker of bone resorption, demonstrated "a profound reduction in bone resorption" appearing rapidly and similarly after the first treatment in the cross-over group, and after the seventh treatment in the long-term treatment group – with the "characteristic attenuation observed at the end of the dosing period," Dr. Brown said.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group. Fracture incidence also remained low in the long-term group in the extension trial, he said, noting that adverse events and serious adverse events also did not increase over time in the extension trial, and there were no "significant imbalances between the groups."

Osteonecrosis of the jaw occurred in two patients in both the long-term and crossover treatment groups; in the crossover group, both cases resolved completely within the follow-up period, and one of those patients had continued on treatment. The cases in the long-term treatment group remained unresolved at the time of Dr. Brown’s report.

These interim findings from the FREEDOM extension trial demonstrate that denosumab treatment for up to 6 years lead to continued improvement in women on long-term treatment, and that treatment for up to 3 years in the crossover group largely reproduced the observations in the original FREEDOM denosumab group, Dr. Brown concluded.

Dr. Brown disclosed having various relationships with Abbott, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier, and Warner Chilcott. Other authors on the study also disclosed various relationships with these and/or other pharmaceutical companies.

CHICAGO – Denosumab remained well-tolerated, safe, and effective for maintaining reduced bone turnover and for increasing bone mineral density after 6 years of continuous use in 2,343 postmenopausal women with increased fracture risk due to osteoporosis.

These findings come from the first 3 years of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis) extension trial.

The fully human monoclonal antibody also led to significant gains in bone mineral density in a "crossover" group of 2,207 women who received placebo during the original FREEDOM trial – a pivotal trial published in 2009 that demonstrated a favorable risk/benefit profile for denosumab (N. Engl. J. Med. 2009;361:756-65).

The agent subsequently received Food and Drug Administration approval for the treatment of postmenopausal women with osteoporosis and an increased fracture risk.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group.

During the open-label active treatment extension trial, which was designed to investigate the efficacy and safety of the drug for up to 10 years, participants received 60 mg of denosumab as a subcutaneous injection every 6 months along with daily supplemental calcium and vitamin D. In the first 3 years of the extension trial, those in the long-term treatment group experienced additional, statistically significant increases in bone mineral density (cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip), and those in the crossover group experienced significant mean gains in bone mineral density that were similar to those seen initially in the FREEDOM trial active treatment group (9.4% at the lumbar spine and 4.8% at the total hip), Dr. Jacques P. Brown reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

The gains seen in the active treatment group in the FREEDOM trial at 3 years were 10.1% at the lumbar spine and 5.7% at the total hip, said Dr. Brown of Laval University, Quebec City.

Measures of serum carboxy-terminal telopeptide (CTX), which is a marker of bone resorption, demonstrated "a profound reduction in bone resorption" appearing rapidly and similarly after the first treatment in the cross-over group, and after the seventh treatment in the long-term treatment group – with the "characteristic attenuation observed at the end of the dosing period," Dr. Brown said.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group. Fracture incidence also remained low in the long-term group in the extension trial, he said, noting that adverse events and serious adverse events also did not increase over time in the extension trial, and there were no "significant imbalances between the groups."

Osteonecrosis of the jaw occurred in two patients in both the long-term and crossover treatment groups; in the crossover group, both cases resolved completely within the follow-up period, and one of those patients had continued on treatment. The cases in the long-term treatment group remained unresolved at the time of Dr. Brown’s report.

These interim findings from the FREEDOM extension trial demonstrate that denosumab treatment for up to 6 years lead to continued improvement in women on long-term treatment, and that treatment for up to 3 years in the crossover group largely reproduced the observations in the original FREEDOM denosumab group, Dr. Brown concluded.

Dr. Brown disclosed having various relationships with Abbott, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier, and Warner Chilcott. Other authors on the study also disclosed various relationships with these and/or other pharmaceutical companies.