Tarsa: Novartis's fracture data do not bode well for Ostora

Novartis's SMC021 has failed to meet its main fracture reduction endpoint in a Phase III trial for osteoporosis. This is a setback for other firms aiming to stimulate the class's growth, such as Tarsa, which may now struggle to bring its pipeline drug Ostora to the market. Novartis is expected to discontinue the development of SMC021 and focus on more attractive targets for osteoporosis treatment.

Novartis's oral salmon calcitonin SMC021 has failed to meet its primary and secondary endpoints in a pivotal Phase III study of postmenopausal osteoporosis. Study 2303 failed to demonstrate a significant difference between treatment groups at three years for the primary endpoint of reducing new vertebral fractures. Similarly, no statistically significant response was observed on key secondary endpoints such as new non-vertebral fractures or new clinical fractures. Companies developing calcitonins will not welcome the news.

Salmon calcitonins have been used to treat osteoporosis for over two decades, but are not commonly used due to poorer efficacy than other more popular therapies, such as bisphosphonates. Reducing fractures is the primary goal of therapy, but calcitonins have historically lacked strong efficacy for this endpoint. While the negative data from the SMC021 trial are perhaps unsurprising, they will further heighten the perception that calcitonins have lower efficacy.

Novartis, a leading company in the osteoporosis space, was developing SMC021 as the first oral alternative to its injectable/inhalable Miacalcic (salmon calcitonin) using Emisphere's proprietary oral delivery technology. Tarsa is developing another Phase III salmon calcitonins candidate, Ostora. Both companies were hoping to revive the class by leveraging the wealth of safety data available for calcitonins following the recently exposed long-term safety issues seen with bisphosphonates and other classes.

At the 2011 Society of Bone and Mineral Research Annual Meeting, Tarsa had presented data showing that Ostora was able to significantly increase bone mineral density (BMD) in Phase III clinical trials. However, as an increase in BMD does not appear to guarantee fracture prevention, the company needed a positive outcome from Novartis's fracture trial of SMC021, which would suggest a class effect.

The failure of SMC021 to meet its endpoints is a major setback for the companies aiming to stimulate the growth of the calcitonin class. Datamonitor believes that it is unlikely that Novartis will continue the development of SMC021, and that it will instead focus its resources on developing more attractive targets for osteoporosis, such as its Phase II antisclerostin candidate BPS-804. Additionally, Tarsa is now likely to have trouble finding a partner that can bring Ostora to the marketplace.