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ACTIVE: Abaloparatide reduces fracture risk in postmenopausal women with osteoporosis

Postmenopausal women with osteoporosis assigned once-daily abaloparatide injection experienced a lower rate of vertebral and nonvertebral fractures during 18 months vs. those assigned teriparatide or a placebo, according to results from a randomized controlled trial.

“This new medication, abaloparatide, can build bone mass very quickly in both the spine and the hip which are the two most important sites for osteoporosis-related fractures,” Felicia Cosman, MD, medical director of the clinical research center at Helen Hayes Hospital, senior clinical director of the National Osteoporosis Foundation and professor of medicine at Columbia University, told Endocrine Today. “The result of this bone building is a rapid reduction in the occurrence of fractures in both the spine as well as the rest of the skeleton. This represents a great potential treatment for osteoporosis-afflicted patients for the future.”

Felicia Cosman

Felicia Cosman

Cosman, Paul D. Miller, MD, FACP, medical director of the Colorado Center for Bone Research, and colleagues , and colleagues analyzed data from 2,463 menopausal women participating in the ACTIVE trial, a phase 3, double blind, randomized controlled study conducted at 28 sites in 10 countries (mean age, 69 years). Participants had a bone mineral density T-score of up to –2.5 and greater than –5 at the lumbar spine or femoral neck, together with evidence of at least two mild vertebral fractures or one moderate vertebral fracture, or a low-trauma fracture of the forearm, humerus, sacrum, pelvis, hip, femur or tibia within 5 years. Women older than 65 years without fracture history were included if BMD T-score was –3 or less and at least –5 at the lumbar spine or femoral neck (mean femoral neck T-score, –2.1). Researchers assigned women to daily injections of abaloparatide (Radius Health; 80 µg; n = 824); open-label teriparatide (Forteo, Eli Lilly; 20 µg; n = 818) or placebo (n = 821) for 18 months. The primary endpoint was the percentage of women with new vertebral fractures in the abaloparatide vs. placebo groups; secondary endpoints included BMD change at total hip, femoral neck and lumbar spine and time to first incident of vertebral fracture in the abaloparatide vs. placebo groups.

Researchers found that participants in the abaloparatide group experienced fewer morphometric vertebral fractures during the study period (n = 4; 0.58%) vs. the teriparatide group (n = 6; 0.84%) and placebo group (n = 30; 4.22%). Comparing abaloparatide with placebo, the RR for new vertebral fracture was 0.14 (95% CI, 0.05-0.39); HR for nonvertebral fracture was 0.57 (95% CI, 0.32-1).

When compared with placebo, participants assigned to abaloparatide also saw increases in BMD from baseline during the 18-month period at the total hip (4.18% vs. –0.1%), femoral neck (3.6% vs. –0.43%) and lumber spine (11.2% vs. 0.63%).

Serious, treatment-emergent adverse events were similar between abaloparatide, teriparatide and placebo groups (9.7%, 10% and 11%, respectively). Overall incidence of hypercalcemia was lower in the abaloparatide group vs. teriparatide group (3.4% vs. 6.4%) at any time during the study. Researchers did not observe evidence of increased cardiovascular risk associated with hypercalcemia in the abaloparatide group.

Cosman noted that the findings apply to women with a fracture history, as well as those with very low bone mass who have not had fractures; however, more research is needed on the drug’s effect on other groups.

“We need to continue evaluate abaloparatide in other clinical settings,” Cosman said. “We would like to see if this medication is just as efficatious in men, for example, and how efficatious it is in people who have been on other osteoporosis therapies.”

Drug developer Radius Health submitted a new drug application to the FDA for abaloparatide on March 30. The company submitted a marketing authorization application in Europe on Nov. 17.

“We are honored to have these findings published in JAMA, and are encouraged by the totality of data collected to date which demonstrate that abaloparatide, if approved, could have a significant impact in improving outcomes for women with postmenopausal osteoporosis,” Lorraine A. Fitzpatrick, MD, chief medical officer of Radius, said in a press release. “We look forward to presenting additional scientific information about abaloparatide as part of the American Society for Bone Mineral Research (ASBMR) Annual Meeting in Atlanta, Georgia September 16-19, 2016.” – by Regina Schaffer

Disclosure: The study was funded by Radius Health. Miller reports serving on scientific advisory boards for AgNovos, Amgen, Eli Lilly, Merck, Radius Health, Roche, and Ultragenyx; receiving research grants from Alexion, Amgen, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Immunodiagnostics, Merck, Merck Serono, National Bone Health Alliance, Novartis, Radius Health, Regeneron, Roche Diagnostics and Ultragenyx; and serving on data safety committees for Allergan and the Grunenthal Group. Please see the full study for the other authors’ relevant financial disclosures.

Postmenopausal women with osteoporosis assigned once-daily abaloparatide injection experienced a lower rate of vertebral and nonvertebral fractures during 18 months vs. those assigned teriparatide or a placebo, according to results from a randomized controlled trial.

“This new medication, abaloparatide, can build bone mass very quickly in both the spine and the hip which are the two most important sites for osteoporosis-related fractures,” Felicia Cosman, MD, medical director of the clinical research center at Helen Hayes Hospital, senior clinical director of the National Osteoporosis Foundation and professor of medicine at Columbia University, told Endocrine Today. “The result of this bone building is a rapid reduction in the occurrence of fractures in both the spine as well as the rest of the skeleton. This represents a great potential treatment for osteoporosis-afflicted patients for the future.”

Felicia Cosman

Felicia Cosman

Cosman, Paul D. Miller, MD, FACP, medical director of the Colorado Center for Bone Research, and colleagues , and colleagues analyzed data from 2,463 menopausal women participating in the ACTIVE trial, a phase 3, double blind, randomized controlled study conducted at 28 sites in 10 countries (mean age, 69 years). Participants had a bone mineral density T-score of up to –2.5 and greater than –5 at the lumbar spine or femoral neck, together with evidence of at least two mild vertebral fractures or one moderate vertebral fracture, or a low-trauma fracture of the forearm, humerus, sacrum, pelvis, hip, femur or tibia within 5 years. Women older than 65 years without fracture history were included if BMD T-score was –3 or less and at least –5 at the lumbar spine or femoral neck (mean femoral neck T-score, –2.1). Researchers assigned women to daily injections of abaloparatide (Radius Health; 80 µg; n = 824); open-label teriparatide (Forteo, Eli Lilly; 20 µg; n = 818) or placebo (n = 821) for 18 months. The primary endpoint was the percentage of women with new vertebral fractures in the abaloparatide vs. placebo groups; secondary endpoints included BMD change at total hip, femoral neck and lumbar spine and time to first incident of vertebral fracture in the abaloparatide vs. placebo groups.

Researchers found that participants in the abaloparatide group experienced fewer morphometric vertebral fractures during the study period (n = 4; 0.58%) vs. the teriparatide group (n = 6; 0.84%) and placebo group (n = 30; 4.22%). Comparing abaloparatide with placebo, the RR for new vertebral fracture was 0.14 (95% CI, 0.05-0.39); HR for nonvertebral fracture was 0.57 (95% CI, 0.32-1).

When compared with placebo, participants assigned to abaloparatide also saw increases in BMD from baseline during the 18-month period at the total hip (4.18% vs. –0.1%), femoral neck (3.6% vs. –0.43%) and lumber spine (11.2% vs. 0.63%).

Serious, treatment-emergent adverse events were similar between abaloparatide, teriparatide and placebo groups (9.7%, 10% and 11%, respectively). Overall incidence of hypercalcemia was lower in the abaloparatide group vs. teriparatide group (3.4% vs. 6.4%) at any time during the study. Researchers did not observe evidence of increased cardiovascular risk associated with hypercalcemia in the abaloparatide group.

Cosman noted that the findings apply to women with a fracture history, as well as those with very low bone mass who have not had fractures; however, more research is needed on the drug’s effect on other groups.

“We need to continue evaluate abaloparatide in other clinical settings,” Cosman said. “We would like to see if this medication is just as efficatious in men, for example, and how efficatious it is in people who have been on other osteoporosis therapies.”

Drug developer Radius Health submitted a new drug application to the FDA for abaloparatide on March 30. The company submitted a marketing authorization application in Europe on Nov. 17.

“We are honored to have these findings published in JAMA, and are encouraged by the totality of data collected to date which demonstrate that abaloparatide, if approved, could have a significant impact in improving outcomes for women with postmenopausal osteoporosis,” Lorraine A. Fitzpatrick, MD, chief medical officer of Radius, said in a press release. “We look forward to presenting additional scientific information about abaloparatide as part of the American Society for Bone Mineral Research (ASBMR) Annual Meeting in Atlanta, Georgia September 16-19, 2016.” – by Regina Schaffer

Disclosure: The study was funded by Radius Health. Miller reports serving on scientific advisory boards for AgNovos, Amgen, Eli Lilly, Merck, Radius Health, Roche, and Ultragenyx; receiving research grants from Alexion, Amgen, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Immunodiagnostics, Merck, Merck Serono, National Bone Health Alliance, Novartis, Radius Health, Regeneron, Roche Diagnostics and Ultragenyx; and serving on data safety committees for Allergan and the Grunenthal Group. Please see the full study for the other authors’ relevant financial disclosures.

    Perspective

    The randomized controlled trial by Miller and colleagues assessed the effect of a new parathyroid hormone-related protein analog (abaloparatide) on new vertebral fractures in postmenopausal osteoporotic women. Women treated with the abaloparatide had seven times less vertebral fractures and two times less non-vertebral fractures. Abaloparatide produced a greater increase in bone mineral density than placebo and had a low incidence of hypercalcemia compared with teriparatide; keeping in mind that this comparison was not double-blinded. The advantage of abaloparatide is a possible higher anabolic action on bone compared with teriparatide. The study is interesting and assesses the clinical effect of an osteoanabolic agent that has probably less risk of atypical femur fractures or jaw osteonecrosis. Some limitations exist. Similarly, as for teriparatide studies, the study is short (18 months) and does not say if the effect lasts after that period. The authors conclude the treatment is effective but needs further research to understand the clinical importance of the reported risk reduction and more information on benefits/risks and the efficacy of abaloparatide vs. bisphosphonates.

    Reference:

    Meier RP, et al. Arch Intern Med. 2012;doi:10.1001/archinternmed.2012.1796.

    • Raphael P. H. Meier, MD, PhD
    • Department of Surgery University Hospital of Geneva, Faculty of Medicine

    Disclosures: Meier reports no relevant financial disclosures.