Oral Recombinant Parathyroid Hormone

In July 2008, Emisphere announced that its partner, Novartis Pharma AG, launched a Phase I study in postmenopausal women to determine the safety and tolerability of an oral formulation PTH-1-34, a combination of human PTH-1-34 and the absorption enhancer 5-CNAC using Emisphere's proprietary Eligen® Technology, for the treatment of postmenopausal osteoporosis. The study was designed to assess the bioavailability profile of increasing doses of PTH-1-34 combined with different amounts of 5-CNAC administered orally. On October 19, 2009, Novartis reported results of this study which showed potentially relevant therapeutic exposure and safety profiles similar to those of the currently available injectable dosage form. These were presented at the 73rd Annual Scientific Meeting of the American College of Rheumatology in Philadelphia, PA.

In April 2010, Novartis initiated a second Phase I trial for an oral PTH-1-34 for the treatment of postmenopausal osteoporosis. The study is a partially blinded, placebo controlled, active comparator study to explore the safety, tolerability, pharmacokinetics and pharmacodynamics in postmenopausal women after daily doses of PTH-1-34. The study has two parts (A and B) and will enroll approximately 120 women. In Part A ascending doses of oral PTH-1-34 will be tested for safety, tolerability and pharmacokinetics and compared to Forsteo®. In Part B, in addition to safety and tolerability of oral PTH, pharmacodynamic responses will be measured by bone biomarker levels and bone mineral density and compared to Forsteo®.

Recombinant PTH, has been approved for the treatment of osteoporosis, which is a disease associated with a gradual thinning and weakening of the bones that occurs most frequently in women after menopause.. PTH is produced by the parathyroid glands to regulate the amount of calcium and phosphorus in the body. When PTH is used therapeutically, it has been shown to increase bone strength and density, which in turn helps to prevent fractures. At this time, PTH is available only by injection.

On June 17, 2011, Novartis informed us of the results of its recently completed Proof of Concept study for an oral PTH1-34 using Emisphere's Eligen® Technology in post-menopausal women with osteoporosis or osteopenia. Novartis informed us that although the study confirmed that oral PTH1-34 was both safe and well-tolerated, several clinical endpoints were not met. Based on the data analyzed, Novartis has terminated the study and anticipates no further work on oral formulation of PTH1-34.