Tarsa’s Oral Calcitonin—TBRIA™

Calcitonin is a naturally occurring hormone in vertebrates that is involved in regulating calcium in the body. Pharmaceutical formulations of calcitonin contain salmon calcitonin, which is about 30 times more potent than human calcitonin. The safety and efficacy of calcitonin in the treatment of osteoporosis in postmenopausal women, as well as in the bone disorder Paget’s disease, are historically long-established.

When calcitonin is released into the bloodstream, it binds to receptors located on bone cells known as osteoclasts, which are responsible for the resorption (breaking down) of existing bone in an ongoing physiologic process of remodeling that replaces old bone with newly synthesized bone. Once calcitonin binds to its receptor it temporarily inhibits bone resorption by the osteoclasts. This physiologic role of calcitonin is the basis for its pharmacologic use in the treatment of osteoporosis.

Calcitonin: A Long History of Use

Salmon calcitonin products have been on the market for over 35 years in the U.S., with few reports of serious safety issues. During this period there have been no literature reports of calcitonin-suspected atypical femur fractures or osteonecrosis of the jaw, adverse events that have been associated with the most commonly used class of osteoporosis therapies, the bisphosphonates.

Calcitonin (via injection or a nasal spray) has demonstrated efficacy and safety in the treatment of osteoporosis in postmenopausal women; injectable calcitonin is also indicated in the bone disorder Paget’s disease.

TBRIA™: The First Oral Calcitonin

Like other peptides, calcitonin would normally be digested by gastrointestinal enzymes if administered orally. Therefore previous use of calcitonin has been limited to administration by injection or nasal spray. TBRIAemploys proprietary technology allowing for once-daily oral delivery of calcitonin by preventing this degradation and assisting the transit of calcitonin across the cells lining the intestine and into the bloodstream. Oral administration of calcitonin may provide a more convenient route of administration for patients with postmenopausal osteoporosis who are candidates for calcitonin therapy (i.e., when alternative treatments are not suitable or for those who refuse other therapeutics.) Oral administration may also result in better patient compliance.

Phase III ORACAL Data

The full efficacy and safety data from the Phase III ORACAL trial were published in the JBMR and were also presented at the American Society for Bone and Mineral Research (ASBMR) 2011 Annual Meeting. These data showed that in postmenopausal women with osteoporosis, TBRIA was superior to both placebo and nasal calcitonin spray in increasing bone mineral density (BMD) at the lumbar spine after 48 weeks. In the trial, the safety profile of TBRIA did not differ substantially from either nasal calcitonin or placebo. The majority of adverse events (AEs) were mild or moderate and consistent with the known safety profile of calcitonin. The most commonly reported AEs were gastrointestinal, and occurred with a similar frequency in the TBRIA and placebo arms of the study.  In this study, TBRIA was significantly less immunogenic than nasal calcitonin spray, meaning that fewer patients who received oral calcitonin developed antibodies directed against calcitonin. Whether this will translate into a clinical benefit for TBRIA versus conventional calcitonin is unknown at this time.

Tarsa is seeking the same indication for TBRIA as calcitonin nasal spray:  Treatment of postmenopausal osteoporosis in women greater than 5 years postmenopause when alternative treatments are not suitable (e.g., osteoporosis patients for whom other therapies are contraindicated or for patients who are intolerant or unwilling to use other therapies). Fracture reduction efficacy has not been demonstrated.

Tarsa has also completed a Phase II study that evaluated the ability of TBRIA to improve BMD at the lumbar spine in women with osteopenia at increased risk of fracture. In this trial, TBRIA produced statistically significant improvements in BMD at the lumbar spine, and its safety profile did not differ substantially from placebo. These data were presented at the ASBMR 2012 Annual Meeting and published in Osteoporosis International. Tarsa is considering future development options for this indication.