Phase III: Oral Calcitonin Scores for Osteoporosis

SAN DIEGO – A novel once-daily oral calcitonin tablet hit all of its efficacy and safety end points in a phase III clinical trial for treatment of postmenopausal osteoporosis.

The oral formulation of recombinant salmon calcitonin, known as Ostora, proved significantly more effective at building bone mineral density than conventional nasal calcitonin in the 18-site, multinational, double-blind, double-placebo ORACAL trial, Dr. Neil Binkley reported at the annual meeting of the American Society for Bone and Mineral Research.

ORACAL involved 565 postmenopausal women with osteoporosis and a mean age of 66 years. They were randomized 4:3:2 to once-daily bedtime therapy with oral calcitonin at 200 mcg, conventional nasal calcitonin at 200 IU, or placebo.

The absolute change in lumbar spine bone mineral density at 48 weeks – the primary study end point – showed a relatively modest 1.5% increase in the oral calcitonin group. But this was significantly greater than the 0.8% increase with the commercially available nasal calcitonin, which in turn was significantly better than the placebo response.

Potential safety issues with the bisphosphonates and other currently available medications have led many osteoporosis patients to decline therapy, while other women stop treatment due to side effects. Calcitonin, in contrast, has a 30-year history of safe prescription use via the intranasal and injectable routes. An oral formulation "might improve convenience and compliance with calcitonin therapy," observed Dr. Binkley, an endocrinologist at the University of Wisconsin, Madison.

Salmon calcitonin is an analog of human calcitonin that’s 30- to 50-fold more potent in suppressing osteoclast resorption.

In the ORACAL trial, levels of CTx (C-terminal telopeptide), a biomarker of bone resorption, dropped by 30% in the oral calcitonin group at 48 weeks, compared with 11% reductions in the nasal calcitonin and placebo arms.

Only 6.5% of women assigned to oral calcitonin developed anticalcitonin antibodies, compared with 32.5% of those on nasal calcitonin. This suggests delivery of the agent via the gastrointestinal tract is less immunogenic than the nasal mucosa. In any case, the production of antibodies had no apparent impacts on safety or efficacy, the endocrinologist continued.

The side effect picture in the oral and nasal calcitonin groups mirrored that in placebo-treated controls.

Tarsa Therapeutics, which is developing oral calcitonin, estimates at least 2 million American women have discontinued osteoporosis treatment. The company plans to file with the Food and Drug Administration for marketing approval later this year and with the European regulatory agency next year.

In addition, the company is developing oral calcitonin for the prevention of osteoporosis in postmenopausal women with osteopenia. A double-blind phase II trial is underway.

Dr. Binkley disclosed he has received a research grant from Tarsa, which sponsored the phase III trial.

SAN DIEGO – A novel once-daily oral calcitonin tablet hit all of its efficacy and safety end points in a phase III clinical trial for treatment of postmenopausal osteoporosis.

The oral formulation of recombinant salmon calcitonin, known as Ostora, proved significantly more effective at building bone mineral density than conventional nasal calcitonin in the 18-site, multinational, double-blind, double-placebo ORACAL trial, Dr. Neil Binkley reported at the annual meeting of the American Society for Bone and Mineral Research.

ORACAL involved 565 postmenopausal women with osteoporosis and a mean age of 66 years. They were randomized 4:3:2 to once-daily bedtime therapy with oral calcitonin at 200 mcg, conventional nasal calcitonin at 200 IU, or placebo.

The absolute change in lumbar spine bone mineral density at 48 weeks – the primary study end point – showed a relatively modest 1.5% increase in the oral calcitonin group. But this was significantly greater than the 0.8% increase with the commercially available nasal calcitonin, which in turn was significantly better than the placebo response.

Potential safety issues with the bisphosphonates and other currently available medications have led many osteoporosis patients to decline therapy, while other women stop treatment due to side effects. Calcitonin, in contrast, has a 30-year history of safe prescription use via the intranasal and injectable routes. An oral formulation "might improve convenience and compliance with calcitonin therapy," observed Dr. Binkley, an endocrinologist at the University of Wisconsin, Madison.

Salmon calcitonin is an analog of human calcitonin that’s 30- to 50-fold more potent in suppressing osteoclast resorption.

In the ORACAL trial, levels of CTx (C-terminal telopeptide), a biomarker of bone resorption, dropped by 30% in the oral calcitonin group at 48 weeks, compared with 11% reductions in the nasal calcitonin and placebo arms.

Only 6.5% of women assigned to oral calcitonin developed anticalcitonin antibodies, compared with 32.5% of those on nasal calcitonin. This suggests delivery of the agent via the gastrointestinal tract is less immunogenic than the nasal mucosa. In any case, the production of antibodies had no apparent impacts on safety or efficacy, the endocrinologist continued.

The side effect picture in the oral and nasal calcitonin groups mirrored that in placebo-treated controls.

Tarsa Therapeutics, which is developing oral calcitonin, estimates at least 2 million American women have discontinued osteoporosis treatment. The company plans to file with the Food and Drug Administration for marketing approval later this year and with the European regulatory agency next year.

In addition, the company is developing oral calcitonin for the prevention of osteoporosis in postmenopausal women with osteopenia. A double-blind phase II trial is underway.

Dr. Binkley disclosed he has received a research grant from Tarsa, which sponsored the phase III trial.

SAN DIEGO – A novel once-daily oral calcitonin tablet hit all of its efficacy and safety end points in a phase III clinical trial for treatment of postmenopausal osteoporosis.

The oral formulation of recombinant salmon calcitonin, known as Ostora, proved significantly more effective at building bone mineral density than conventional nasal calcitonin in the 18-site, multinational, double-blind, double-placebo ORACAL trial, Dr. Neil Binkley reported at the annual meeting of the American Society for Bone and Mineral Research.

ORACAL involved 565 postmenopausal women with osteoporosis and a mean age of 66 years. They were randomized 4:3:2 to once-daily bedtime therapy with oral calcitonin at 200 mcg, conventional nasal calcitonin at 200 IU, or placebo.

The absolute change in lumbar spine bone mineral density at 48 weeks – the primary study end point – showed a relatively modest 1.5% increase in the oral calcitonin group. But this was significantly greater than the 0.8% increase with the commercially available nasal calcitonin, which in turn was significantly better than the placebo response.

Potential safety issues with the bisphosphonates and other currently available medications have led many osteoporosis patients to decline therapy, while other women stop treatment due to side effects. Calcitonin, in contrast, has a 30-year history of safe prescription use via the intranasal and injectable routes. An oral formulation "might improve convenience and compliance with calcitonin therapy," observed Dr. Binkley, an endocrinologist at the University of Wisconsin, Madison.

Salmon calcitonin is an analog of human calcitonin that’s 30- to 50-fold more potent in suppressing osteoclast resorption.

In the ORACAL trial, levels of CTx (C-terminal telopeptide), a biomarker of bone resorption, dropped by 30% in the oral calcitonin group at 48 weeks, compared with 11% reductions in the nasal calcitonin and placebo arms.

Only 6.5% of women assigned to oral calcitonin developed anticalcitonin antibodies, compared with 32.5% of those on nasal calcitonin. This suggests delivery of the agent via the gastrointestinal tract is less immunogenic than the nasal mucosa. In any case, the production of antibodies had no apparent impacts on safety or efficacy, the endocrinologist continued.

The side effect picture in the oral and nasal calcitonin groups mirrored that in placebo-treated controls.

Tarsa Therapeutics, which is developing oral calcitonin, estimates at least 2 million American women have discontinued osteoporosis treatment. The company plans to file with the Food and Drug Administration for marketing approval later this year and with the European regulatory agency next year.

In addition, the company is developing oral calcitonin for the prevention of osteoporosis in postmenopausal women with osteopenia. A double-blind phase II trial is underway.

Dr. Binkley disclosed he has received a research grant from Tarsa, which sponsored the phase III trial.