Long-Acting Parathyroid Hormone Analog for the Treatment of Hypoparathyroidism

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The primary symptoms of hypoparathyroidism include muscle cramping, convulsions, intellectual disabilities, cataracts and abnormal heart rhythm. Symptoms are due to low serum calcium (hypocalcemia). Replacement of parathyroid hormone (PTH) has been explored to remedy the calcium deficiency, but maintaining an optimal calcium level has proven problematic because hypercalcemia can occur as a result of excess PTH. Multiple efforts are under way targeting either full-length PTH (PTH 184) or the active amino-terminal domain (PTH 134), but these molecules have undesirable pharmacokinetic properties for chronic daily management of calcium levels in patients with hypoparathyroidism. Eli Lilly scientists have identified a PTH receptor modulator (PTH-RM) that can normalize serum calcium. At fairly low doses, the PTH-RM was shown to normalize calcium levels in parathyroidectomized rats, with a profile similar to basal insulin use in patients with diabetes. The investigators are collaborating with TRND to develop this PTH-RM toward a Phase II proof-of-concept study for hypoparathyroidism by leveraging the existing data package. TRND scientists, in collaboration with researchers from Eli Lilly & Company and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), have further developed the animal model of hypoparathyroidism to generate robust efficacy data. With concurrence from the U.S. Food and Drug Administration (FDA), the team will execute the full preclinical development plan. TRND will support the preparation and filing of the Investigational New Drug (IND) Application with the FDA, with NICHD providing support for subsequent clinical trials in patients.