ZT-031, a cyclized analog of parathyroid hormone(1-31) for the potential treatment of osteoporosis.

Abstract

ZT-031 is a cyclic 31-amino acid analog of parathyroid hormone (PTH) that is in development by Zelos Therapeutics Inc for the treatment of osteoporosis and other bone-related disorders. ZT-031 activates the PTH type 1 receptor - the molecular target of the currently marketed osteogenic peptides PTH and PTH(1-34). Daily subcutaneous injections of ZT-031 prevented bone loss and replaced bone that had already been lost in an ovariectomized rat model of osteoporosis. Daily subcutaneous injections of ZT-031 in gonad-intact monkeys increased bone mineral density (BMD) at cortical and cancellous bone sites and increased serum levels of bone formation markers. The daily subcutaneous administration of ZT-031 to postmenopausal women with osteoporosis elicited a dose-dependent increase in BMD of the lumbar spine, proximal femur and total hip area. Plasma levels of bone formation markers were significantly increased above baseline after 1 month of dosing, and prior to increases in bone resorption markers. ZT-031 was demonstrated to be safe and well tolerated; episodes of hypercalcemia were infrequent and observed with a frequency greater than with placebo only at the highest doses tested for the drug. Although available data are limited, the results obtained following treatment with ZT-031 have generally been at least as favorable as those obtained with other osteogenic PTH peptides. A novel dosing paradigm has been planned for the drug.